Possible involvement of calcitonin gene-related peptide (CGRP) in non-cholinergic non-adrenergic relaxation induced by mesenteric nerve stimulation in guinea pig ileum.

Mesenteric nerve (MN) stimulation produced a biphasic response, i.e., a contraction followed by a prolonged relaxation in the isolated guinea pig ileum after complete adrenergic neuron blockade with guanethidine. This biphasic response mimicked the effect of capsaicin by itself. The latter relaxation response to MN stimulation was unaffected by hexamethonium, but was abolished by capsaicin in an irreversible fashion. Calcitonin gene-related peptide desensitization (CGRP-D) reduced the relaxation response to about 20% of the control. After pretreatment with atropine and guanethidine, MN stimulation provoked a pure relaxation, which was significantly reduced to about 20% of the control by CGRP-D. Therefore, it seems likely that the non-adrenergic non-cholinergic relaxation response to MN stimulation is partly mediated via a release of CGRP from sensory nerve endings.