Capsaicin-induced inhibition of motility of the rat isolated vas deferens: do multiple neuropeptides mediate the visceromotor effects of capsaicin?

1 The effects of capsaicin have been investigated in the field-stimulated (0.1 Hz) or unstimulated rat isolated vas deferens and compared with those of some neuropeptides (neurokinins, calcitonin gene-related peptide (CGRP) putatively stored in capsaicin-sensitive sensory fibres. 2 Capsaicin (0.01-3 microM) produced a concentration-related transient inhibition of the field-stimulation-induced twitches. This effect was characterized by marked desensitization and could not be elicited in preparations excised from capsaicin-pretreated rats (50 mg/kg s.c., 4 days before). The amplitude of the nerve-mediated twitches was unaffected by capsaicin-desensitization. 3 Neurokinins (substance P, Kassinin) produced a potentiation of the nerve-mediated contractions while CGRP had a potent inhibitory effect. In the presence of Kassinin, CGRP still inhibited twitches although the time course of this inhibitory effect was delayed as compared to controls. 4 In the unstimulated rat vas deferens neither capsaicin (3 microM) nor CGRP (0.1 microM) had any significant motor effect. However, when phasic contractions were initiated by previous exposure to Kassinin (0.2 microM), both capsaicin (3 microM) or CGRP (10-100 nM) had a prompt inhibitory effect. Capsaicin inhibition exhibited a marked desensitization while the effect of CGRP was still evident after capsaicin-desensitization. 5 The inhibitory effect of capsaicin or CGRP on the Kassinin-stimulated rhythmic contractions of the rat isolated vas deferens was unaffected by a previous exposure to tetrodotoxin (0.5 microM). 6 Storage at 4 degrees C for 24 h produced a 65% reduction of the response of the rat isolated vas deferens to nerve-stimulation. The residual response was tetrodotoxin-sensitive and could be potentiated by Kassinin (0.2 microM) or inhibited by CGRP (10-100 nM) as observed in controls. In these preparations the inhibitory effect of capsaicin (3 microM) was significantly reduced (approximately equal to 50%) and in some preparations abolished, as compared to controls. 7 These findings indicate the existence, in the rat isolated vas deferens, of capsaicin-sensitive sensory innervation which, upon chemical stimulation, releases, through a tetrodotoxin-insensitive mechanism, a substance(s) which inhibits motility at postjunctional level. CGRP is a possible candidate for the role of inhibitory sensory transmitter released from capsaicin-sensitive nerve endings in this preparation.