Antagonism of the effects of calcitonin gene-related peptide and of capsaicin on the guinea-pig isolated ileum by human alpha-calcitonin gene-related peptide(8-37).
The possible mediating role of calcitonin gene-related peptide (CGRP) in the effects of capsaicin in the guinea-pig ileum has been investigated by means of the CGRP antagonist hCGRP(8-37). Submaximal longitudinal muscle relaxation of the histamine-precontracted ileum evoked by rat CGRP (3 nM) or capsaicin (1 microM) was reversed by hCGRP(8-37) (1.5 microM), while that due to adrenaline or neurotensin was not affected. Inhibition of spontaneous circular muscle movements by capsaicin (100 nM) was also reversed by hCGRP(8-37). The CGRP antagonist had no effect on electrical stimulation-evoked ileal contractions or on the longitudinal or circular muscle tone. It is concluded that (a) hCGRP(8-37) is a specific CGRP antagonist in the ileum, apparently devoid of intrinsic activity or any effect not related to CGRP; (b) the inhibitory actions of capsaicin on the longitudinal and circular muscles of the ileum are mediated, at least in part, by CGRP.
Barthó
L
L
Department of Pharmacology, Medical School of Pécs, Hungary.
Kóczán
G
G
Holzer
P
P
Maggi
C A
CA
Szolcsányi
J
J
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002211:Capsaicin / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D001285:Atropine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin