Propagation of impulses in the guinea-pig ureter and its blockade by calcitonin gene-related peptide (CGRP).
The guinea-pig ureter was placed in a three-compartment organ bath to enable the application of electrical stimuli or drugs to its renal end (R-site), the middle region (M-site) or the bladder end (B-site) while recording mechanical activity at the R- and B-sites. All experiments were performed in ureters pre-exposed to capsaicin (10 microM for 15 min) to prevent the release of sensory neuropeptides from afferent nerves. Electrical field stimulation (EFS, 5-25 ms pulse width, 20 V) produced a phasic contraction at the site of stimulation ('direct' response to EFS) which propagated to the other end of the ureter. Section of the ureter at the M-site abolished the propagated response to EFS; after section, EFS applied at the M-site induced a phasic contraction at both the R- and B-sites. Likewise, the application of KCl at the M-site produced phasic contractions at both the R- and B-sites. Tetrodotoxin (1 microM), nifedipine (1 microM) or Bay K 8644 (1 microM) applied at the M-site had no influence on the direct or propagated responses to EFS; nifedipine (10 microM) applied at the M-site abolished the propagated responses without affecting the direct responses to EFS. Bay K 8644 (1 microM) applied at the R-site produced a marked enhancement of the direct response (EFS applied at R-site) while having no effect on the amplitude of the propagated response to EFS.(ABSTRACT TRUNCATED AT 250 WORDS)
Meini
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Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Santicioli
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Maggi
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D019806:Cromakalim; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects* / Q000502:physiology*
D001578:Benzopyrans; D011758:Pyrroles; D019806:Cromakalim; D013779:Tetrodotoxin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D015740:Calcitonin Gene-Related Peptide; D005905:Glyburide