PT  - JOURNAL ARTICLE
AU  - Edwards, R M
AU  - Stack, E J
AU  - Trizna, W
TI  - Calcitonin gene-related peptide stimulates adenylate cyclase and relaxes intracerebral arterioles.
DP  - 1991 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1020--1024
VI  - 257
IP  - 3
4099  - http://jpet.aspetjournals.org/content/257/3/1020.short
4100  - http://jpet.aspetjournals.org/content/257/3/1020.full
SO  - J Pharmacol Exp Ther1991 Jun 01; 257
AB  - The effects of calcitonin gene-related peptide (CGRP) on lumen diameter and adenylate cyclase activity in isolated intracerebral arterioles were examined. CGRP produced a concentration-dependent relaxation of spontaneous tone developed by the arterioles with an EC50 value of 3.9 x 10(-9) M. Calcitonin, as well as substance P, which is frequently colocalized with CGRP, had no effect on arteriolar tone. CGRP also relaxed arterioles contracted with the thromboxane mimetic, U-44619, yielding an EC50 value of 3 x 10(-9) M. The CGRP fragment, human CGRP(8-37), antagonized CGRP-induced relaxation in a noncompetitive manner. Adenylate cyclase activity in single arterioles was stimulated by CGRP, but not by substance P, in a concentration-dependent fashion. Half maximal stimulation occurred at 8 x 10(-9) M, whereas maximum stimulation (2.5-fold over basal) occurred at 10(-7) M. CGRP(8-37) inhibited CGRP-stimulated adenylate cyclase activity over a concentration range of 10(-9) to 10(-5) M. The results demonstrate that CGRP stimulates adenylate cyclase activity and is a potent vasodilator of small parenchymal cerebral arterioles in vitro and may play an important role in the regulation of cerebral blood flow.