Second messengers are intracellular signaling molecules that are released within cells in response to extracellular first messengers like hormones and neurotransmitters. They amplify and propagate intracellular signals. Examples include cyclic AMP (cAMP), cyclic GMP (cGMP), inositol trisphosphate, and calcium. cAMP and cGMP are produced from ATP and GTP by adenylate and guanylate cyclases, respectively. They activate downstream effector proteins like protein kinase A and G. This leads to phosphorylation of various target proteins and physiological responses like metabolism, gene expression, cell survival, proliferation and apoptosis. The document discusses the mechanisms, targets, functions and therapeutic applications of cAMP and cGMP second messenger systems in detail.
MAPK Signaling pathway (Mitogen-activated protein kinase), how the pathway helps in regulation of mitosis, It's activation and inactivation inside the cell, roles of MAPK pathway in cancerous cell, different classes of MAP kinase in human
MAPK Signaling pathway (Mitogen-activated protein kinase), how the pathway helps in regulation of mitosis, It's activation and inactivation inside the cell, roles of MAPK pathway in cancerous cell, different classes of MAP kinase in human
An introductory overview of drug regulation in the biotch industry. Provides and intro to cGMP, FDA Inspections and Logistics and Drug Regulation History in the U.S.
This is a presentation that I developed and gave to the GMP constituency of a medium-sized biopharmaceutical company to satisfy one of the requirements for ongoing cGMP training. I feel that it very well epitomizes one of my central philosophies surrounding GXP and regulatory topic training -- STORYTELLING.
Bionext Pharma Pvt. Ltd., a dedicated manufacturing facility for Liquid Orals is pledged to Ethics for manufacturing of quality drug products that consistently meet the standards by adhering to current Good Manufacturing Practices (cGMP) in its facility, it also endeavors to delight the customers through its unique and cost effective formulations and timely quality services? .
Good Manufacturing Practice, or GMP, is a set of practices and systems that are aimed at making sure that pharmaceutical products are manufactured in conformance with set requirements and standards. The aim of GMP also referred to sometimes as cGMP or Current Good Manufacturing Practice, is to ensure that there is control and consistency in the pharmaceutical products, so that the processes used for controlling quality and consistency of the product can be traced back in the event of a problem.
1.Receptors Link to other Enzymatic Activity.
2.Pathway of Intracellular Signal Transduction.
3.The Cyclic AMP pathway4.Cyclic GMP pathway
5.Phospholipids and Ca2+
6.The PI3-Kinase /Akt and mTOR pathways.
7.MAP Kinase Pathway.
This Slide gives you a idea about the subject Cellular and Molecular pharmacology where the cell signalling, secondary messengers and its intracellular signalling pathways has been celarly explained
Signal transducing machinery as targets for potential drugs.
Drugs:-
a). Diclofenac- for treating cholera toxin
b). Fasentin- for treating insulin signalling
General principles of signal transduction
G Protein-coupled Receptors (GPCRs): Structure and Mechanism.
GPCRs that Regulate Adenylyl Cyclase.
GPCRs that Activate Phospholipase C.
GPCRs that Regulate Ion Channels.
GPCRs that Regulate Gene Transcription.
Cell signaling / Signal Transduction / Transmembrane signaling.
It is the process by which cells communicate with their environment and respond to external stimuli.
When a signaling molecule(ligand) binds to its receptor, it alters the shape or activity of the receptor, triggering a change inside of the cell such as alteration in the activity of a gene / cell division. Thus the original Intercellular Signal is converted into an Intracellular Signal that triggers as a response.
Cell signaling is part of any communication process that governs basic activities of cells and coordinates all cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis
CNS Introduction, Neurons, Type of Neurons and functions, Neuroglia and types, Receptors and their types, Synapse, Neurotransmitters and their functions
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
2. secondMESSENGERS
Second messengers are intracellular signaling
molecules released by the cell to trigger physiological
changes such as proliferation, differentiation, migration,
survival, and apoptosis.
Second messengers are therefore one of the initiating
components of intracellular signal
transduction cascades.
3. Examples of second messengers include cyclic AMP,
cyclic GMP, Inositol trisphosphate, Diacylglycerol
and Calcium.
Releases in response to exposure to extracellular
signaling molecules/ligands the first messenger, such
as neurotransmitters, hormones (epinephrine,
growth hormone and serotonin).
4. The first messengers such as peptide hormones,
neurotransmitters usually do not physically cross the
phospholipid bilayers.
First messengers need to be transduced into
secondary messengers, so that the extracellular signal
may be propagated intracellularly.
5. Second messengers greatly amplify the strength of the
signal.
Activate or inhibit the target enzymes of the pathway.
6. History
Earl Wilbur Sutherland Jr. discovered secondary
messengers.
He saw that epinephrine stimulate glycogenolysis in liver
cells, but epinephrine alone would not convert glycogen to
glucose
He found that epinephrine had to trigger a secondary
messenger, cyclic AMP for the liver to convert glycogen to
glucose. He won the 1971 Nobel Prize in Medicine.
7. Common mechanisms of second messenger
systems
There are several different secondary messenger systems
(cAMP system, phosphoinositol system), but they all are
quite similar in overall mechanism, although the
substances involved and overall effects can vary.
8.
9. Types Of SecondMessenger Molecules
Three basic types of second messenger
molecules:
Hydrophobic molecules:
membrane-associated e.g.
diacylglycerol, phosphatidylinositol
Hydrophilic molecules: water-
soluble molecules, such as cAMP,
cGMP, IP3, and Ca2+, located
within the cytosol.
Gases: nitric oxide (NO), carbon
monoxide (CO) and hydrogen
sulfide (H2S) which can diffuse both
through cytosol and across cellular
membranes.
10. 1. cAMP
cAMP is a second
messenger, synthesized
from ATP by enzyme
adenylyl cyclase.
Adenylate cyclase is
activated by stimulatory
G (Gs)-protein-coupled
receptors.
Inhibited by adenylate
cyclase inhibitory G
(Gi)-protein-coupled
receptors.
11. Cyclic AMP generated by adenylyl cyclases has three
major targets in most cells,
The cyclic AMP dependent protein kinase (PKA),
cAMP-regulated guanine nucleotide exchange factors
termed EPACs (exchange protein directly activated by
cAMP), and
via PKA phosphorylation, a transcription factor termed
CREB (cAMP response element binding protein).
12. PKA REGULATION by cAMP
The most common downstream
effector of cAMP is Protein kinase
A(PKA).
PKA is normally inactive as
tetrameric holoenzyme(two catalytic
and two regulatory units).
The regulatory unit always block the
catalytic center of catalytic unit.
Two cAMP molecules bind to each
PKA regulatory subunit.
The regulatory subunit dissociate from
the catalytic subunit.
The free catalytic subunits interact
with proteins to phosphorylate Ser or
Thr residues, thus producing cellular
response.
13. PKA can phosphorylate a diverse array of
physiological targets such as metabolic enzymes and
transport proteins, and numerous regulatory proteins
including other protein kinases, regulation
of glycogen, sugar, and lipid metabolism, ion
channels, and transcription factors.
14. cAMP Response Element-Binding (CREB)Protein
Cellular transcription factor e.g. the neurotrophin
BDNF, tyrosine hydroxylase & many neuropeptides
binds to certain DNA sequences called cAMP response
elements (CRE) thereby increasing or decreasing the
transcription of the downstream genes.
15. Protein synthesis-PKA
directly activate CREB,
which bind the cAMP
response element
(CRE). The activated
CREB protein then binds
to a CRE region, and is
then bound
to CBP (CREB binding
protein), which co-
activates it, allowing it to
switch certain genes on or
off and altering the
transcription.
16. CREB has many functions in many different organs,
and some of its functions have been studied in relation
to the brain. CREB proteins in neurons are thought to
be involved in the formation of long-term memories.
CREB is also important for the survival of neurons, as
studied in genetically engineered mice, where CREB
and CREM were deleted in the brain. If CREB is lost
in the whole developing mouse embryo, the mice die
immediately after birth, again highlighting the critical
role of CREB in promoting survival.
17. Cyclic AMP–Regulated Guanine Nucleotide Exchange
Factors
The small GTP-binding proteins are monomeric GTPases
and key regulators of cell function. The small GTPases
operate as binary switches that exist in GTP- or GDP-
liganded conformations. They integrate extracellular signals
from membrane receptors with cytoskeletal changes and
activation of diverse signaling pathways, regulating such
processes as phagocytosis, progression through the cell
cycle, cell adhesion, gene expression, and apoptosis.
18. For example, many small GTPases are regulated by GEFs
(Guanine Nucleotide Exchange Factors). GEFs act by
binding to the GDP-liganded GTPase and catalyzing the
exchange of GDP for GTP.
The two GEFs regulated by cAMP are able to activate
members of the Ras small GTPase family, Rap1 and Rap2;
these GEFs are termed exchange proteins activated by
cyclic AMP (EPAC-1 and EPAC-2). The EPAC pathway
provides an additional effector system for cAMP signaling
and drug action.
19. These pathways play major role in Cell
differentiation/proliferation, cytoskeletal organization,
vesicular trafficking & nuclear transport.
Potential target for cancer therapy.
22. Cyclicnucleotide phosphodiesterases (PDEs)
Cyclic nucleotide phosphodiesterases form another family
of important signaling proteins whose activities are
regulated via the rate of gene transcription as well as by
second messengers (cyclic nucleotides or Ca2+) and
interactions with other signaling proteins such as β arrestin
and protein kinases. PDEs hydrolyze the cyclic 3′,5′-
phosphodiester bond in cAMP and cGMP, thereby
terminating their action.
23. Phosphodiesterase 4 (PDE4) is the predominant cAMP-
degrading enzyme expressed in inflammatory cells.
cAMP helps regulate T cell function.
cAMP helps maintain immune homeostasis by suppressing
the release of proinflammatory mediators (eg, TNF-α, IL-
17, and IFN-γ). cAMP promote the release of anti-
inflammatory mediators (eg, IL-10) by immune cells.
24. Decrease in PDE4 increases cAMP, leads to increased
transcription of genes that have CRE sites, including the
gene for IL-10, which is an anti-inflammatory mediator.
25. PDEs are drug targets for treatment of diseases such as
asthma, COPD, cardiovascular diseases such as heart
failure, atherosclerotic coronary and peripheral arterial
disease, and neurological disorders.
26. Recent Development
A new Second Messenger, c-di-AMP was
discovered in Staphylococcus aureus with a Role in
Controlling Cell Size and Envelope Stress. This work was
published in the September 2011 Issue of PLoS Pathogens.
27. Most of work on c-di-AMP signaling has been done in
Gram-positive bacteria and actinobacteria, where c-di-AMP
signaling pathways affect potassium transport, cell wall
structure, and antibiotic resistance.
These findings greatly expand the c-di-AMP signaling role
and reveal a central metabolic regulatory role for a cyclic
dinucleotide.
However, the molecular mechanisms of c-di-AMP signaling
are still poorly understood.
28. cGMP
The signaling pathways that regulate the synthesis of
cyclic GMP in cells include hormonal regulation of
transmembrane guanylate cyclases such as the atrial
natriuretic peptide receptor (ANP) and the activation
of soluble forms of guanylate cyclase by nitric oxide
(NO).
29. Unlike cAMP, cGMP has established signaling roles in
only few cell types
Signaling pathways that regulate synthesis include:
Nitric Oxide
Hormonal Regulation (ANP/BNP/CNP)
30. Nitric oxide (NO) is a
gas, diffuse through the
plasma membrane and
affect nearby cells.
Synthesized from arginine
and oxygen by the NO
synthase.
NO then activate soluble
guanylyl cyclase, to
produce cGMP.
Nitric Oxide
31. The function of NO is the
dilation of blood vessels.
The acetylcholine
(neurotransmitter) acts on
endothelial cells to
stimulate NO synthesis.
NO, diffuses to
neighboring smooth
muscle cells where it
interacts with the guanylyl
cyclase.
This increase enzymatic
activity resulting in the
synthesis of cGMP.
The cGMP then induces
muscle relaxation and
blood vessel dilation.
32. Nitric Oxide Synthase (NOS) exists as 4 isoforms:
Neuronal type I isoform (nNOS)
Inducible type II isoform (iNOS)
Endothelial type III isoform (eNOS)
Mitochondrial isoform (mtNOS)
33. NOS constitutively expressed in:
eNOS
Endothelium, cardiac myocytes, renal mesangial cells,
osteoblasts, platelets and is involved with regulating
vascular function (Vasodilation).
nNOS
CNS nerves and skeletal muscles, performs a role in cell
communication and is associated with plasma membranes
34. iNOS
Macrophages, Kupffer cells, neutrophils, fibroblasts,
vascular smooth muscle cells & endothelium and involved
in immune defence against pathogens.
mtNOS
NO in the mitochondrial matrix may regulate ATP
synthesis.
35. Natriuretic Peptide
3 small peptide ligands:
Atrial Natriuretic Peptide (ANP)
Brain Natriuretic Peptide (BNP)
C-type Natriuretic Peptide (CNP)
These peptides possess potent natriuretic, diuretic,
and vasodilating activities and are implicated in body fluid
homeostasis and blood pressure control.
36. The major physiological effects of these hormones are to
decrease blood pressure (ANP, BNP), to reduce cardiac
hypertrophy and fibrosis (BNP), and to stimulate long bone
growth (CNP).
37. The transmembrane receptors for ANP, BNP, and CNP
are ligand-activated guanylate cyclases. The ANP and
BNP receptors contain 450 amino acid extracellular
domain that binds the peptide, a short 20 amino acid
transmembrane domain, and large intracellular
domains that contain a kinase homology region, and a
C-terminal guanylate cyclase domain. Phosphorylation
of serine residues in the kinase domain is important for
activity; dephosphorylation of these residues leads to
desensitization of the receptor.
39. Downstream reactions of cGMP:
Activation of Protein Kinase G
cGMP gated ion channels
cGMP-modulated Phosphodiesterase
Pharmacologically important effects of elevated cyclic GMP
include modulation of platelet activation and relaxation of
smooth muscle. PDEs hydrolyze the cyclic 3′,5′-phosphodiester
bond in cAMP and cGMP, thereby terminating their action.
40. Therapeutic Applications
Selected Drugs that target cGMP signalling
Drug cGMP Therapeutic Application
Nitroglycerine NO Donor Angina
Sodium Nitroprusside NO Donor Hypertensive
Emergencies
Nesiritide Synthetic
BNP
Acutely decompensated
CHF
Ecadotril ↑ BNP Congestive Heart Failure
41. BAY Series of
Compounds
BAY 41-2272
8-pCPT-cGMP
Riociguat (Adempas)
Specific
activators &
inhibitors of
PKG
Asthma
Graft survival after liver
& lung transplantation.
Pulmonary Hypertension
The first messengers such as peptide hormones, neurotransmitters typically are hydrophilic molecules, these first messengers may not physically cross the phospholipid bilayer cell membrane to initiate changes within the cell directly—unlike steroid hormones, which usually do .
Hydrophobic molecules: diacylglycerol, phosphatidylinositol, membrane-associated diffuse from the plasma membrane into the intermembrane space where they can reach and regulate membrane-associated effector proteins
How can each GPCR transmit a specific signal even though so many different GPCRs are using the same second messenger?
Brain-derived neurotrophic factor
binds to certain DNA sequences called cAMP response elements (CRE) thereby increasing or decreasing the transcription of the downstream genes
CREB (cAMP response element-binding protein) is a cellular transcription factor
D2 Agonist
NO in the mitochondrial matrix may regulate ATP synthesis.
gram positive and negative bacteria,tumor cells and heterologous antigens; involved in transplantation
Specifically, in smooth muscle tissue, PKG promotes the opening of calcium-activated potassium channels,[2] leading to cell hyperpolarization and relaxation, and blocks agonist activity of phospholipase C, reducing liberation of stored calcium ions by inositol triphosphate.
CNG channels are nonselective cation channels that are found in the membranes of various tissue and cell types, and are significant in sensory transduction as well as cellular development. CNG channels are significant in the function of various sensory pathways including vision and olfaction, as well as in other key cellular functions such as hormone release and chemotaxis.
Riociguat (trade name Adempas) is a novel drug (by Bayer) that is a stimulator of soluble guanylate cyclase (sGC). Clinical trials have looked at riociguat as a new approach to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Riociguat constitutes the first drug of a novel class of sGC stimulators.
Based largely on published and preliminary results from the author's laboratory, particular emphasis is placed on HO- and CO-mediated cyclic GMP signaling and the newly described agents YC-1 and BAY 41-2272 and their positive influence on vascular smooth muscle growth. Description of these novel sGC/cyclic GMP-sensitizing approaches is included along with therapeutic rationale for their use, an area of study that is gaining critical importance in the basic and clinical sciences.
Moreover, the discovery of new cyclic GMP modulating agents such as YC-1 and BAY 41-2272 that operate in NO-independent manner but that augment NO and CO signals provides new routes for cyclic GMP control and sound basis for this novel pharmacotherapeutic regimen.