The document summarizes key aspects of the blood-brain barrier and cholinergic transport. It discusses how the blood-brain barrier tightly regulates passage between blood and brain tissue. It then explains how choline is transported into neurons and acetylated to form acetylcholine, which acts on nicotinic and muscarinic receptors to mediate cholinergic signaling. Specific subtypes of these receptors are described along with their functions and locations in the central and peripheral nervous systems.

1. SEMINAR ON BBB-CHOLINE
TRANSPORTER
PRESENTED BY-ROSHAN M JAIN
(M.PHARM 1ST YEAR)
SUBMITTED TO-
Dr . A . GEETHALAKSHMI
(HOD and Professor of department of
pharmaceutics)
RR COLLEGE OF PHARMACY

2. BLOOD-BRAIN BARRIER
• The blood-brain barrier (BBB) is highly selective permeability
barrier that separates the circulating blood from the brain
extracellular fluid (BECF) in the central nervous system (CNS).
• BBB is a unique membranous barrier that tightly segregates
the brain from the circulating blood .
• The blood-brain barrier acts very effectively to protect the
brain from many common bacterial infections .
• The blood-brain barrier is composed of high density cells
restricting passage of substances from the bloodstream much
more than endothelial cells in capillaries .

3. STRUCTURE OF BBB
• Capillaries of brain are lined with a layer of special
endothelial cells that are sealed with tight junctions .
• These tight junction called zona occludens .
• The blood-brain barrier blocks all molecules except those that
cross cell membranes by means of lipid solubility ( such as
oxygen , carbon dioxide , ethanol , and steroid hormones )
and those that are allowed in by specific transport system
(such as sugar and some amino acids ) .
• Substances with a molecular higher than 500 daltons
generally cannot cross BBB .

4. Blood-Brain Barrier
• The BBB is permeable to small and lipophilic molecules but
larger molecules are not transported across unless there is an
active transport system available .

5. CHOLINERGIC TRANSPORT
• Drugs affecting the ANS are divided into two groups .
According to the types of neurons involved in their
mechanism of action .
 Cholinergics – acts on the receptor stimulated by ach
 Adrenergics – acts on the receptor stimulated by
norepinephrine .

6. CHOLINERGIC AGENTS
• Cholinergic agents are the drugs that act either directly or
indirectly produce effect similar to those by acetylcholine.
• while studying the pharmacological actions of Ach they are
distinguished two types of activities designated as muscarinic
and nicotinic

7. SYSTHESIS OF ACH
• Choline is take up into the nerve terminals by
special choline transport system mediated by a carrier
co transport sodium .
• It can be inhibited by hemicholinium .
• The choline is acetylated by the enzyme called as
choline acetyl transferase to from Ach the acetyl group
source is acetyl-coA .

8. STORAGE AND RELEASE OF ACH
• The Ach is packaged into vesicles by an active transport
process coupled with the efflux of protons .
• The mature vesicles also contain ATP and proteoglycon
channel .
• When an action potential propagated voltage sensitive
calcium channels in the pre synaptic membrane opens causes
an increase in intracellular calcium .
• Elevated calcium levels promote the fusion of synaptic
vesicles with the cell membrane and release of their contents
into the synaptic cleft .
• This release can be blocked by botulinum toxin .
• Ach is degraded by acetylcholinestearse and forms choline
and aceate in the synaptic cleft .

10. CHOLINERGIC RECEPTORS
• Cholinergic receptors have been characterized as nicotinic and
muscarinic on the basis of their ability to be bound by
naturally occurring alkaloids nicotine and muscarine
respectively .
• They are two classes of receptors
MUSCARINIC & NICOTINIC
1. Muscarinic receptors are G protein-coupled receptors .
2. Nicotinic receptors belongs to ligand gated receptors .

11. • SUB TYPES OF MUSCARINIC RECEPTORS :
M 1 , M 2 , M 3 .
• SUB TYPES OF NICOTINIC RECEPTORS :
Nm , Nn .
M1
Location : gastric paracrine gland , CNS , sympathetic ganglia
Functional response : acid secretion
cognitive function (learning & memory)
depolarisation of autonomic ganglia
Agonists : oxotremorine
Antagonists : pirenzepine , telenzepine

12. M2
Location : 1) Heart
2) Smooth muscle
3) Nerve terminal 4) CNS
Functional response : Heart HR
Atria contraction : Ventricle contraction
Smooth muscle contraction
Agonists : Methacholine
Antagonists : Methoctramine , Tripitramine .

13. M3
Location : 1 ) Smooth muscle
2 ) Iris , cilliary muscle
3 ) CNS
Functional response : Smooth muscle contraction
Blood Vessel – relaxation
Pupil constriction , cilliary contraction
Agonists : Bethanechol
Antagonists : Darifenacin

14. NICOTINIC RECEPTOR
• Selectively active by nicotine
ACTIVATION :
• Nicotinic receptor activation
• Opening of channels
• Results rapid flow of cations into the cell
• DEPOLARISATION , Increase ACTION POTENTIAL

15.  Nm : ( skeletal muscle end plate )
• Mediates skeletal muscle contraction .
• Selectively stimulated by PHENYL TRIMETHYL AMMONIUM .
• Blocked by Tubocurarine .
 Nn :
• Located : autonomic ganglia ( depolarisation ) .

16. REFERENCE
• SEAN EKINS.COMPUTER ADDED DRUG
DEVELOPMENT.2018 ;PAGE NO 506 .
• WWW.WIKIPEDIA.COM.
• WWW.SLIDESHARE.COM.