Bicarbonate-dependent action of Bay K 8644 in the smooth muscle of the rat vas deferens.
Effects of Bay K 8644, partial depolarization with high potassium, and nifedipine on the dose-response curves of the rat vas deferens to norepinephrine, methacholine and KCI were investigated in HEPES-buffered physiological salt solution (PSS) with or without 20 mM sodium bicarbonate. In the bicarbonate-containing PSS, Bay K 8644 at 10(-6) M enhanced the maximal contractions in response to norepinephrine, methacholine and KCI by 31.4, 103.3 and 40.1%, respectively. In the bicarbonate-free PSS, where the maximal contractions induced by norepinephrine, methacholine and KCI were 77.5, 75.0 and 68.2% of those in the bicarbonate-containing PSS, respectively. Bay K 8644 did not enhance the maximal contractile response to any of the agonists, although the contractions induced by low concentrations of KCI were increased by Bay K 8644. Increasing the potassium concentration in the PSS from 6 to 20 mM enhanced the maximal contractions in response to norepinephrine and methacholine in the bicarbonate-containing PSS, whereas in the bicarbonate-free PSS, the treatment decreased the contractions. In the two PSSs, nifedipine similarly inhibited the contraction in response to either 10(-5) M norepinephrine or 68 mM KCI. These results suggest that bicarbonate ion modulates the function of the voltage-dependent calcium channel in the smooth muscle of the rat vas deferens.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
N
N
Suzuki
Y
Y
Gomi
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014649:Vas Deferens / Q000187:drug effects
D001639:Bicarbonates; D008688:Methacholine Compounds; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D009638:Norepinephrine