Activities of calcitonin gene-related peptide (CGRP) and related peptides at the CGRP receptor.
In guinea pig pancreatic acini rat calcitonin gene-related peptide (CGRP) increased amylase release 2-fold, salmon calcitonin had an efficacy of only 44% of that of CGRP and [Tyr0]CGRP(28-37) and human calcitonin had no actions. [Tyr0]CGRP(28-37), but not human calcitonin, antagonized the actions of CGRP in pancreatic acini with an IC50 of 3 microM. [Tyr0]CGRP(28-37) produced a parallel rightward shift in the dose-response curve for CGRP-stimulated amylase secretion. The inhibition was specific for CGRP and was reversible. Studies with 125I-CGRP demonstrated that CGRP, salmon calcitonin and [Tyr0]CGRP, but not human calcitonin, interacted with CGRP receptors on pancreatic acini. These results indicate that various CGRP-related peptides demonstrate different relationships between their abilities to occupy the CGRP receptor and to affect biologic activity, with CGRP itself being a full agonist, salmon calcitonin a partial agonist, [Tyr0]CGRP(28-37) a competitive antagonist, and human calcitonin having no actions.
Digestive Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
P N
PN
Maton
T
T
Pradhan
Z C
ZC
Zhou
J D
JD
Gardner
R T
RT
Jensen
D000595:Amino Acid Sequence; D000681:Amylases / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D008969:Molecular Sequence Data; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*
D007457:Iodine Radioisotopes; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D000681:Amylases; D015740:Calcitonin Gene-Related Peptide