The role of sensory neuropeptides in motor innervation of the hamster isolated urinary bladder

In this study we have characterized the role of sensory fibers and of the s ensory peptides, neurokinin A (NKA) and calcitonin gene-related peptide (CG RP), on the contractile responses evoked by single pulse electrical field s timulation (EFS) in the hamster urinary bladder. EFS of the hamster isolated urinary bladder produced twitch contractions wh ich were unaffected by atropine but abolished by tetrodotoxin. The P-2 puri noreceptor antagonist PPADS (30 muM) inhibited twitches by 66 +/-4% on its own and by 78 +/-3% in the presence of atropine. The selective tachykinin N K2 receptor antagonist nepadutant produced a slight but consistent reductio n of twitch amplitude (-21 +/-3%) at 1 muM. Addition of nepadutant to atrop ine and PPADS did not further increase their inhibitory effect. The application of hCGRP (10-300 nM) produced a concentration-dependent inh ibition of twitches (E-max -38 +/-3%, EC50=12 nM) and a small reduction of tone (0.5 +/-0.09 mN). Similar effects were obtained with capsaicin (0.1-10 muM) which inhibited EFS-evoked contractions with an EC50 of 100.0 nM and a maximal effect of 34 +/-4% inhibition at 1 muM. Under submaximal parameters of stimulation NKA (10 nM) increased the amplit ude of twitches by 45 +/-6% and produced a concentration-dependent tonic co ntraction (EC50=55.9 nM). The CGRP(1) receptor subtype antagonist, hCGRP(8- 37), increased by 29 +/-8% the EFS-evoked contractions and significantly re duced the response to 0.1 muM CGRP. Capsaicin (10 muM) increased both CGRP- LI and NKA-LI release from superfused slices of hamster urinary bladder by about sixfold and by about 70%, over baseline, respectively. A second appli cation of capsaicin was ineffective, indicating a complete desensitization of sensory nerve efferent function. In the hamster urinary bladder the sensory neuropeptides NKA and CGRP are c o-released by sensory fibers after stimulation either by EFS or capsaicin. However, the role of CGRP appears functionally predominant.