Participation of cAMP in the facilitatory action of beta,gamma-methylene ATP on the noradrenaline release from rabbit ear artery.
beta, gamma-Methylene ATP (betagamma-mATP) significantly facilitated the electrically (4 Hz) evoked release of noradrenaline (NA) from the rabbit ear artery by activation of prejunctional purinoceptors on the sympathetic nerve terminals. In the present study, we investigated whether intracellular cAMP is involved in the purinoceptor mediated facilitatory mechanisms. Forskolin, an adenylate cyclase activator, and 8-bromo cAMP, a cAMP analogue, significantly enhanced the NA-release. The enhancement of NA-release by betagamma-mATP was significantly potentiated by Ro20-1724, a phosphodiesterase inhibitor, but abolished by SQ22536, an adenylate cyclase inhibitor. Both drugs alone had no effect on the NA-release. N-ethylmaleimide and pertussis toxin, inhibitors of Gi-proteins, did not affect the NA-release, or the enhancement of NA-release by betagamma-mATP. Alone Cholera toxin (CTX), an activator of Gs-proteins, significantly increased the NA-release, but in the presence of CTX, betagamma-mATP could not produce further enhancement of the NA-release. These results suggest that cAMP is closely associated with the facilitatory action of betagamma-mATP on NA-release in the rabbit ear artery.
Ishii-Nozawa
R
R
Department of Clinical Pharmacology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan. reiko-in@my-pharm.ac.jp
Shinozuka
K
K
Kunitomo
M
M
Hashimoto
T
T
Takeuchi
K
K
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004357:Drug Synergism; D004423:Ear / Q000098:blood supply*; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011817:Rabbits
D000067956:Adenylyl Cyclase Inhibitors; D010726:Phosphodiesterase Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D000255:Adenosine Triphosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000225:Adenine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine