title: Effect of KATP channel openers on myogenic and neurogenic responses in goat urinary bladder.
abstract: Isolated goat detrusor muscle exhibited spontaneous contractility with an irregular amplitude and frequency. The spontaneity of detrusor muscle exhibited a mean amplitude as 11.99 +/- 0.83 mm and frequency as 1.37 +/- 0.16/min. KATP-channel openers namely, cromakalim or pinacidil (10(-7) - 10(-4) M) added cumulatively, elicited a concentration-related inhibition of both amplitude and rate of spontaneous contractions. The mean IC50 values for both amplitude and frequency for cromakalim were 3.3 x 10(-6) M and 2.9 x 10(-6) M, respectively; and for pinacidil were 2.0 x 10(-5) M and 1.5 x 10(-5) M, respectively. Glibenclamide, a KATP-channel blocker inhibited the cromakalim-induced concentration-related relaxation of spontaneous contractions with a significant increase in its mean IC50. ACh-induced concentration-related contractile response was inhibited in the presence of either cromakalim (10(-4) M) or pinacidil (10(-4) M). The mean EC50 value of ACh, in the presence of cromakalim (2.5 x 10(-3) M) was significantly increased as compared to the control (1.2 x 10(-6) M). In the presence of glibenclamide (10(-5) M) the inhibitory effect of cromakalim was significantly reduced with consequent decrease in the EC50 value (1.9 x 10(-5) M). Application of EFS (30 V and 5 ms) on goat urinary bladder strips at 1, 2, 5, 10, 20 and 30 Hz elicited frequency-related contractile responses. Both cromakalim and pinacidil caused a rightward shift in the frequency-related contractile response curve with significant increase in the mean EF25 and EF50 values, respectively. In the presence of glibenclamide (10(-4) M), the frequency-related inhibitory response curve was shifted to left with significant (P < 0.001) increase in the mean EF25, EF50 and EF75. The present results suggest that in the goat detrusor muscle, agonist and EFS-induced contractile responses were more potently inhibited by cromakalim than pinacidil with activation of glibenclamide sensitive KATP channels.
authors: Department of Pharmacology and Toxicology, Faculty of Veterinary Sciences and Animal Husbandry, Orissa University of Agriculture and Technology, Bhubaneswar 751 003, India.
authors: C
authors: C
authors: Vijayakumar
authors: K
authors: K
authors: Kathirvel
authors: K K
authors: KK
authors: Sardar
authors: S C
authors: SC
authors: Parija
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006041:Goats / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D020110:Pinacidil / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
chemical_list: D018678:Cholinergic Agents; D018727:Muscarinic Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019806:Cromakalim; D020110:Pinacidil; D001285:Atropine; D000109:Acetylcholine; D005905:Glyburide