Attenuation of low pH-, but not capsaicin- or PGI2-evoked CGRP-release by endothelium removal using saponin.
The aim of the present study was to evaluate the role of the endothelium in low pH-, capsaicin-, and prostacyclin (PGI2)-evoked release of calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) from C-fibre afferents in the isolated, perfused guinea-pig heart. CGRP-LI release, and formation of the stable PGI2-metabolite 6-keto-PGF1 alpha, in response to moderate acidosis (pH 7, 6, but not 5) were significantly reduced after removal of endothelium using saponin (50 micrograms mL-1) perfusion. In contrast, the release of CGRP-LI evoked by capsaicin (10(-7) M) or PGI2 (10(-5) M) remained unchanged after removal of the endothelium. Saponin treatment did not influence the vasodilator action of CGRP, whereas the vasodilation evoked by substance P (SP) was abolished. It is concluded that CGRP release evoked by low pH, but not that evoked by capsaicin or exogenous PGI2, is partly endothelium dependent. Our data suggest that endothelially produced PGI2 is involved in low pH-evoked release of CGRP from capsaicin sensitive nerves in the heart.
Källner
G
G
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
Franco-Cereceda
A
A
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D012503:Saponins; D011464:Epoprostenol; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D002211:Capsaicin