The role of extracellular Ca2+ in carbachol-induced tonic contraction of the pig detrusor smooth muscle.
The role of extracellular Ca2+ in the tonic-contractile response to muscarinic receptor stimulation was investigated in isolated detrusor smooth muscle from the pig urinary bladder. Carbachol (10(-8)-10(-5) M) produced a concentration-dependent contractile response in isolated pig detrusor smooth muscle strips consisting of an initial phasic component followed by a tonic component. During the plateau of the tonic contractions induced by carbachol at the submaximal concentration of 10(-6) M, the inhibiting effects of atropine, EGTA, nifedipine (a voltage-dependent calcium channel antagonist), H-7 [a protein kinase C (PKC) inhibitor] and YM934 (a potassium channel opener) on the contractions were evaluated. Atropine (10(-10)-3 x 10(-8) M) concentration-dependently inhibited the tonic contractions induced by carbachol. In the same experimental conditions, EGTA (4 mM) and nifedipine (10(-9)-3 x 10(-7) M) depressed the tonic contractions in a concentration-dependent manner as did H-7 (10(-5)-3 x 10(-5) M) and YM934 (10(-8)-10(-6) M). However, H-7 (10(-5)-3 x 10(-5) M) and YM934 (10(-6) M) were very weak in inhibiting the contractions induced by KCl (50 mM) in isolated pig detrusor smooth muscle strips. These results suggest that the tonic-contractile response induced by carbachol in pig detrusor smooth muscle strips is dependent mainly on depolarization of the cell membranes and an influx of extracellular Ca2+, and also suggest that this depolarizing response may be due to inactivation of ATP-sensitive potassium channels through muscarinic activation of PKC.
Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research, Ibaraki, Japan.
W
W
Uchida
N
N
Masuda
Y
Y
Shirai
K
K
Shibasaki
N
N
Satoh
T
T
Takenada
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D048588:Benzoxazines; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D013552:Swine
D048588:Benzoxazines; D003497:Cyclic N-Oxides; D010078:Oxazines; D015221:Potassium Channels; D011189:Potassium Chloride; D001285:Atropine; D002217:Carbachol; D011493:Protein Kinase C; D009543:Nifedipine; D002118:Calcium; C084963:2H-1,4-benzoxazine, 3,4-dihydro-2,2-dimethyl-6-nitro-4-(2-pyridinyl)-, N-oxide