CHOLECYSTOKININ & Substance P

CHOLECYSTOKININ

-Cholecystokinin is produced in duodenum causing contraction of gall bladder.
-Popularly known as pancreozymin.
-When administered by IV injection causes increase in secretion of
Pancreatic enzymes and also stimulates gall bladder contraction.
-It is used as diagnostic aid for the purpose of testing pancreatic
function along with SECRETIN.
-It is also used as adjunct in cholecystography.
-Vasomotor reactions, abdominal discomfort and hypersensitivity has
been reported.
-Cholecystokinin is a Neuropeptide (octapeptide)
-cholecystokinin receptors are a group of G-protein coupled receptors.
-Antagonists to neuropeptide CCK proved to possess anxiolytic activity.
-*Loxiglumide is CCK antagonist.

SUBSTANCE.P

Substance .P is a neuropeptide .
It is a short chain with 11 amino acid polypeptide.
It functions as Neurotransmitter and neuromodulator.
It belongs to Tachykinin Family, Neuropeptide family.
In body it is majorily synthesized in CNS, bloodvessels, GIT, always and skin.
In CNS substance.P has been associated in regulation of mood
disorders, anxiety, stress, nausea, emesis, pain, respiratory rhythm,
neurogenesis and neurotoxicity.
Tachykinin Family includes NKA,NKB(NK-neurokinin) and Substance. P

*Pharmacological actions-
Action on Blood vessels-
It is a potent vasodilator.
This cause release of Nitric oxide from endothelium causing hypotension.
Action on Neurons-
Substance.P involved in transmission of pain impulses from peripheral
receptors to CNS.
Action on Vomiting center-
Vomiting center in brainstem (medulla oblongata).
Action on smooth muscle-
Causes contraction of smooth muscle and constriction of blood vessel.

*Substance P as a Pain Mediator-
It is a protein found in brain and spinal cord associated with
inflammatory process in joints.
-low back pain
- fibromyalgia
-Arthritis

Physiological Activities-
Vomiting reflex
Defensive behavior
Change in cardiovascular tone
Stimulation of salivary secret
Smooth contraction
Vasodilatation.

Receptors for Substance.P
The endogenous receptor for substance.p is NK-1, NK-1R.
These are G-protein receptors.
Treatment-
Capsaicin obtained from capsicum has been shown to reduce the levels
of substance p in nerve endings and decrease in pain by depletion of
c-fibre nerves.
Antagonist- Aprepitant
Structure- Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2.