Earl Wilbur Sutherland Jr. discovered cyclic AMP (cAMP) as a second messenger that allows hormones like epinephrine to trigger physiological responses in cells. cAMP is produced from ATP by adenylate cyclase in response to hormone binding and activates protein kinase A. Protein kinase A then phosphorylates other proteins to initiate downstream cellular effects. The actions of cAMP are terminated by phosphodiesterase breaking it down and by dephosphorylation of proteins. cAMP mediates many important processes like glycogen breakdown and gene transcription.

1. PRESENTED BY – SMRUTI RANJAN MASANTA
M.PHARM(1ST YR)
PHARMACOLOGY

2. Content
 History
 Introduction
 Secondary messenger
 Hormones uses cyclic AMP Pathway
 Steps of cyclic AMP Pathway
 Termination of cyclic AMP Pathway
 Effect of cyclic AMP Pathway
 Therapeutic application
 Reference

3. History
 Earl Wilbur Sutherland Jr.
discovered second
messengers won the 1971
Nobel Prize in Medicine.
 He saw that epinephrine
would stimulate the liver to
convert glycogen to glucose in
liver cells, but epinephrine
alone would not convert
glycogen to glucose.
 He found that epinephrine
had to trigger a second
messenger, cyclic AMP for the
liver to convert glycogen to
glucose.
Earl Wilbur Sutherland Jr.
(1915-1974)

4. Introduction
 Cyclic AMP is a cyclic nucleotide, Chemically it is a 3’5’
adenosine monophosphate.
 It is synthesized in tissues from ATP under influence
of ADENYLYL CYCLASE in presence of Mg ion.
 It is degraded to 5’AMP by Phosphodiesterase.
 It is a Second Messenger.

5. Second messenger
 Secondary messengers are
intracellular signaling molecules
released by the cell to trigger
physiological changes. it amplify
intracellular signal transduction
cascades.
e.g.- cyclic AMP, cyclic GMP,
inositol trisphosphate(IP3),
diacylglycerol(DAG), calcium.
 First messengers need to be
transduced into secondary
messengers, so that the extracellular
signal may be propagated intra
cellularly.

6. Hormones uses cyclic AMP Pathway
Activate adenylyl cyclase Inhibit adenylyl cyclase
 Epinephrine(β1,β2)
 Norepinephrine
 Glucagon
 CRH
 ACTH
 MSH
 TSH
 AVP/ADH
 HCG
 LH
 FSH
 Somatostatin
 Acetylcholine M2
 Angiotensin II
 Epinephrine α2

7. Steps involve
 Step1 : Binding of ligand to a specific
receptor in the cell membrane.
 Step2: Activation of G-Protein: after
the formation of complex, GDP is
replaced by GTP.
 Step3: Activation of enzyme
ADENYLATE CYCLASE: activated G-
protein either stimulates or inhibits the
enzyme adenylate cyclase which is
located in plasma membrane.
 Step4: Formation of cAMP: when
adenylyl cyclase activated it catalyses
the formation of cAMP from cytoplasmic
ATP with Mg2+ as cofactor. Thus a
stimulatory G-protein increases the
cAMP level whereas inhibitory G protein
decreases the cAMP level.
 Step5: Action of cAMP: it activates
protein kinase A. PKA then
phosphorylate other proteins which
gives rise to cascade of mechanism leads
to cell response.

8. Termination of cyclic AMP
 The actions of cAMP in the cell are terminated in two
ways:
 cAMP is degraded to 5’-AMP in the cell by the
cytoplasmic enzyme Phosphodiesterase(PDE).
 Specific phosphatases dephosphorylates the protein
already phosphorylated by PKA.

10. G-protein activate adenylyl cyclase

14. Effects of cAMP Pathway
 ALTERED GLYCOGEN METABOLISM BY ENZYME
REGULATION
 ALTERED GENE TRANSCRIPTION
 HORMONE ESTRADIOL SECRETION
 ALTERED ION TRANSPORT - HCL SECRETION IN
STOMACH
 WATER REABSORPTION BY ANTI DIURETIC
HORMONE

20. Therapeutic application

22. References
 www.slideshare.com
 www.youtube.com
 www.ncbi.nlm.nih.gov
 www.sciencedirect.com