The effects of Bay K 8644 and nifedipine on the responses of rat urinary bladder to electrical field stimulation, beta,gamma-methylene ATP and acetylcholine.
1. Bay K 8644 (0.33 nM to 1 microM) greatly increased the contractions of rat urinary bladder detrusor muscle induced by beta, gamma-methylene ATP (beta, gamma-MeATP, 10 microM) and by electrical field stimulation of the purinergic component (the cholinergic response was blocked by atropine). 2. The contractions induced by acetylcholine (ACh, 10 microM) and by electrical field stimulation of the cholinergic component (the purinergic response was blocked following desensitization by alpha, beta-MeATP) were also potentiated by Bay K 8644, although to a lesser extent than the purinergic responses. 3. Nifedipine (1 nM to 3.3 microM) inhibited all the contractions induced by beta, gamma-MeATP, ACh and electrical field stimulation. However, while the responses to beta, gamma-MeATP and electrical field stimulation of the purinergic component were almost abolished, a substantial proportion of the responses to ACh and electrical field stimulation of the cholinergic component were nifedipine resistant. 4. The concentration-effect curves for the potentiation by Bay K 8644 of the responses to beta, gamma-MeATP, ACh and electrical field stimulation were shifted to the right by nifedipine (10 nM). At concentrations greater than 1 microM, Bay K 8644 inhibited contraction. 5. It is concluded that voltage-sensitive calcium channels play an important role in the excitatory mechanical action of P2X-purinoceptor-mediated purinergic responses in the rat urinary bladder, while cholinergic-mediated responses are less dependent on such channels.
Bo
X N
XN
Department of Anatomy and Developmental Biology, University College London.
Burnstock
G
G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D001743:Urinary Bladder / Q000187:drug effects*
C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; D009543:Nifedipine; D000109:Acetylcholine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate