Abstract
1. We have investigated the effect of calcitonin gene-related peptide (CGRP) on non-adrenergic, non-cholinergic (NANC) excitatory transmission to the longitudinal muscle of the guinea-pig proximal colon. 2. In the presence of atropine (0.3 microM), guanethidine (5 microM), hexamethonium (100 microM) and indomethacin (3 microM), electrical field stimulation (EFS, 1 Hz, 0.3 ms for 10 s) produced tetrodotoxin-(300 nM)-sensitive contractions which were reduced by the combined administration of FK 888 (10 microM) and MEN 10,376 (0.3 microM), to block tachykinin NK1 and NK2 receptors, respectively. Thus, the EFS-induced NANC contractions are a tachykinin-mediated response. 3. CGRP, at concentrations higher than 0.1 nM, caused an increase in the electrically-evoked, NANC contractions in a concentration-dependent manner and at 10 nM produced a maximal effect (pEC50 = 9.20 +/- 0.17, n = 6). 4. 5-Hydroxytryptamine (5-HT, 1-100 nM) also caused an increase in the EFS-induced NANC contractions in a concentration-dependent manner and at 30 nM produced a maximal effect (pEC50 = 8.06 +/- 0.09, n = 4), but calcitonin (10-100 nM) failed to enhance the EFS-induced NANC responses. Moreover, a 5-HT4 receptor antagonist, DAU 6285 (3 microM) abolished the enhancing action of 5-HT (30 nM). 5. The combined administration of FK 888 (10 microM) plus MEN 10,376 (0.3 microM) abolished the enhancement of EFS-induced NANC contractions by CGRP (10 nM), but DAU 6285 (3 microM) had no effect on the enhancement.(ABSTRACT TRUNCATED AT 250 WORDS)
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