Influence of Calcitonin Gene-related Peptide Release on pH-induced Mechanical Depression in Rat Atria.

Abstract

SUMMARYRat atria is richly innervated by sensory nerve fibers that release CGRP when stimulated either by capsaicin or acid pH. We studied the physiological relevance of acid pHinduced CGRP release on changes in atrial contractility and relaxation produced by lowering the pH. Isolated atria electrically paced at 2.77 Hz were exposed to a 10-minute period of metabolic acidosis (pH=6.73±0.01, n=28) after: 1) CGRP release induced by capsaicin 0.5 µM; 2) blockage of CGRP release with ruthenium red (RR) 5 µM; 3) no pretreatment; and 4) CGRP receptor blockage with CGRP 8-37 1 µM. Contractility and relaxation were significantly less depressed by acid pH when CGRP release was prevented by RR or CGRP receptor activation was blocked by CGRP . The results suggest that CGRP release and the activation of CGRP receptors may be physiologically involved in contributing to the depression of contractility and relaxation induced by acid pH in rat atria. (Jpn Heart J 2001; 42: 507-517)

Transient Receptor Potential Vanilloid-1 Channels Contribute to the Regulation of Acid- and Base-Induced Vasomotor Responses

“…In addition, several receptors have also been identified as acid-base sensors on nonneural (e.g., G protein-coupled [8] or calcium-sensing receptors [9]) and neural (e.g., acid-sensing ion channels [10]) elements of the vascular wall. Stimulation of these molecules on nerve terminals by changes in local pH results in the release of neural transmitters (e.g., calcitonin gene-related peptide or substance P), which also contribute to the mediation of the vascular response [11,12]. Nevertheless, the vascular biology concerning the molecular nature of the acid-base sensors is not fully clarified, and it is also largely unknown whether these receptors are located mainly on neural, nonneural, or perhaps both elements in the vascular wall.…”