Effects of P2-receptor agonists on sympathetic neuroeffector transmission in the rat isolated anococcygeus muscle.
The effects of nicotinamide adenine dinucleotide phosphate (NADPH), alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP), L-beta,gamma-methylene adenosine 5'-triphosphate (L-beta,gamma-MeATP), 2-methylthio-adenosine 5'-triphosphate (MeSATP) and adenosine-5-O-(2'-thiodiphosphate) (ADPbetaS) were investigated on the contractions to electrical field stimulation in the rat anococcygeus muscle. Stimulation-induced contractions were not affected by L-beta,gamma-MeATP (3-100 microM) or MeSATP (3-100 microM), but were enhanced by NADPH (10-100 microM), alpha,beta-MeATP (3-30 microM) and ADPbetaS (3-10 microM) in a concentration-dependent manner, and the enhancements were antagonised by the P2-receptor antagonist suramin (100 microM). The enhancement produced by alpha,beta-MeATP (10 microM) and ADPbetaS (10 microM) was also antagonised by pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (10 microM) and reactive blue 2 (100 microM). The enhancement produced by alpha,beta-MeATP (10 microM) was not altered by NG-nitro-L-arginine methyl ester (100 microM), desipramine (1 microM) or idazoxan (0.1 microM) excluding, respectively, the possible involvement of nitric oxide, neuronal amine uptake or alpha2-autoinhibition of noradrenergic transmission. Contractions elicited by low (0.1 and 0.3 microM) but not by higher (1 and 3 microM) concentrations of exogenously applied noradrenaline were enhanced by alpha,beta-MeATP (10 microM). Neither the resting nor the stimulation-induced effluxes of radioactivity from [3H]-noradrenaline-labelled anococcygeus muscles were affected by alpha,beta-MeATP (10-100 microM). The findings suggest that P2-receptors subserve the enhancing actions of NADPH, alpha,beta-MeATP and ADPbetaS on sympathetic neuroeffector transmission; however, the subtype of P2-receptor involved and its location remain unclear.
Najbar-Kaszkiel
A T
AT
Department of Medical Laboratory Science, RMIT University, Melbourne, VIC, Australia.
Rand
M J
MJ
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019329:Idazoxan / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009249:NADP / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology
D004791:Enzyme Inhibitors; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D013873:Thionucleotides; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; C030812:adenosine 5'-O-(2-thiodiphosphate); D009249:NADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D003891:Desipramine; D019331:NG-Nitroarginine Methyl Ester; D019329:Idazoxan; C008501:2-methylthio-ATP