Calcitonin gene-related peptide selectively increases cAMP levels in the guinea-pig ureter.
Calcitonin gene-related peptide (CGRP, 0.1 microM) and forskolin (10 microM) both produced a time-dependent accumulation of cAMP in homogenates of the guinea-pig ureter, while cromakalim (3 microM) was ineffective. Neither agent did increase the cGMP levels. cAMP accumulation induced by CGRP or forskolin was unchanged by glibenclamide (1 microM). In sucrose gap, the application of forskolin (1-10 microM for 15 s) hyperpolarized the smooth muscle membrane and its effect was greatly enhanced when tested in a low-K+ medium (extracellular K+ reduced from 5.9 to 1.2 mM). The hyperpolarization produced by 10 microM forskolin was reduced and abolished by 1 and 10 microM glibenclamide, respectively, in both normal and low-K+ medium. The present findings demonstrate that CGRP determines a selective cAMP accumulation in the guinea-pig ureter and suggest that elevation of cAMP may be involved in the opening of glibenclamide-sensitive K+ channels in the ureter smooth muscle.
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Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Morbidelli
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Ziche
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Maggi
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D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D019806:Cromakalim; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D005576:Colforsin; D000242:Cyclic AMP; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D005905:Glyburide