Release of substance P- and calcitonin gene-related peptide-like immunoreactivity and motor response of the isolated guinea pig gallbladder to capsaicin

Abstract

The aim of this study was to assess whether a local motor response to capsaicin could be observed in the isolated guinea pig gallbladder and to discover the mechanism involved. Capsaicin produced a contraction of this organ that exhibited desensitization, suggesting a specific action on sensory nerves. In preparations preexposed to capsaicin to produce a functional blockade of the capsaicin-sensitive sensory fibers, the contractile response to field stimulation was unaffected as compared with controls. Tachykinins (substance P and neurokinin A) produced a concentration-related contraction of this organ, neurokinin A being more potent than substance P. Spantide, a tachykinin antagonist, markedly inhibited the capsaicin-induced gallbladder contraction, leaving the atropine-sensitive response to field stimulation unaffected. Calcitonin gene-related peptide (CGRP) produced a concentration-related relaxation, which was tetrodotoxin-resistant, suggesting a direct effect on muscle cells. Repeated administration of CGRP produced desensitization. At this stage, application of capsaicin produced a contractile response much larger than in controls. Both substance P- and CGRP-like immunoreactivity were detected in the guinea pig gallbladder by radioimmunoassay and were significantly reduced after systemic capsaicin desensitization. Capsaicin induced the simultaneous release of substance P- and CGRP-like immunoreactivity from superfused isolated gallbladders. These findings indicate that capsaicin-sensitive nerves in the guinea pig gallbladder can produce a local motor response involving the release of multiple neuropeptides. In the guinea pig gallbladder, tachykinins and CGRP might act as "physiologic antagonists," as observed in other viscera from rats and guinea pigs.