Role of calcitonin gene-related peptide in capsaicin-induced gastric submucosal arteriolar dilation

Abstract

The response of gastric submucosal arterioles to topical (submucosal) application of calcitonin-gene-related peptide (CGRP) or capsaicin with and without the human CGRP antagonist, hCGRP-(8-37), was studied using in vivo microscopy. CGRP (10(-11) to 10(-8) M) induced dose-dependent dilation. Topical treatment with hCGRP(8-37) (10(-6) M, for 10 min) caused a significant decrease in basal arteriolar diameter from 33 +/- 2 to 27 +/- 2 microns. hCGRP(8-37) did not alter acetylcholine- or adenosine-induced vasodilation but did significantly reduce CGRP 10(-8) M vasodilation from 97.3 +/- 10.1 to 15.9 +/- 4.4% of the maximal response. Topical capsaicin (10(-9) M to 5 x 10(-7) M) induced dose-dependent arteriolar dilation. This vasodilation was markedly attenuated by hCGRP(8-37). Selective ablation of capsaicin-sensitive sensory neurons nearly completely inhibited capsaicin-induced vasodilation, suggesting that this vasodilation is primarily neurogenic in origin. We conclude that 1) topical application of capsaicin stimulates capsaicin-sensitive sensory neurons and induces dose-dependent arteriolar dilation; 2) this vasodilation is mediated in part by CGRP; and 3) CGRP may be involved in modulating the basal tone of gastric resistance vessels.

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

“…Capsaicin, a vanilloid receptor agonist, stimulates capsaicin-sensitive afferent neurons, which releases CGRP and substance P from their nerve endings. [26][27][28][29] In previous reports, Zingiberis rhizoma extract and 6-shogaol produced an increase in intestinal blood flow, and the CGRP receptor antagonist CGRP (8-37) completely abolished the reaction.…”

Vascular bed‐dependent roles of the peptide CGRP and nitric oxide in acid‐evoked hyperaemia of the rat stomach.

“…This conclusion challenges the concept that the acidevoked hyperaemia in the stomach arises solely from axon reflexes between collaterals of afferent nerve fibres within the gastric wall Li et al 1992). There is ample evidence, though, that CGRP is an important neuroeffector transmitter of the vasodilator (Li, Raybould, Quintero & Guth, 1991;Chen, Li & Guth, 1992;Li et al 1992) and protective (Lambrecht, Burchert, Respondek, Muller & Peskar, 1993) effects of afferent nerve stimulation in the rat gastric mucosa. The present results with the CGRP receptor antagonist are in line with another study of the mucosal microcirculation and confirm that in the rat gastric mucosa CGRP is to a large degree responsible for the blood flow increment in response to acid back-diffusion.…”

“…1992;Holzer et al 1993). The dilator effect of the peptide on extramural arteries of the stomach is, like that on the gastric microcirculation (Li et al 1991;Chen et al 1992), antagonized by CGRP(8-37), which indicates that the gastric vasodilator action of CGRP is mediated by CGRP-1 receptors (Dennis et al 1990). CGRP(8-37), however, was less active in inhibiting the acid-evoked hyperaemia in the left gastric artery than the dilator response of this vessel to CGRP.…”

Effects of Ninjin-to on Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

“…Capsaicin, the pungent ingredient in red peppers and a vanilloid receptor agonist, stimulates capsaicin-sensitive afferent neurons, which release CGRP and substance P from their nerve endings. [32][33][34][35] It has been reported that 6-shogaol produces an increase in intestinal blood flow, and that the CGRP receptor antagonist, CGRP (8-37), completely abolishes Ginger rhizome and 6-shogaol-induced hyperemia. 24) Naito et al also reported that plasma CGRP and substance P levels significantly increased after administration of Zingiberis rhizoma extract to healthy subjects.…”