Cyclic AMP antagonizes adenosine-induced inhibition of ganglionic transmission.
The mechanism of adenosine-induced inhibition of ganglionic transmission was investigated in the isolated superior cervical ganglion (SCG) of the rat. The inhibitory effect of adenosine on the postganglionic compound action potential (CAP) was antagonized by pretreatment of ganglia with forskolin, isoproterenol (IPNE), arginine vasopressin (AVP), or papaverine, all of which are known to increase tissue cAMP level by different mechanisms. Furthermore, pretreatment of ganglia with the adenylate cyclase inhibitor SQ 22, 536, or the phosphodiesterase activator imidazole reversed the effects of IPNE and forskolin. Pretreatment with 8-bromo-cAMP, resulted in a marked antagonism of the adenosine-induced inhibition. By themselves, none of these drugs had any significant effect on the CAP. Adenosine slightly but significantly decreased the basal level of cAMP in untreated ganglia. Formation of cAMP induced by IPNE was markedly reduced by adenosine. This was largely reversed in the presence of the adenosine A1 receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) but not the A2 receptor antagonist 3, 7-dimethyl-1-propargylxanthine (DPMX). We conclude that the inhibition of ganglionic transmission by adenosine involves reduction of cAMP formation through activation of A1 receptors.
Hogan
Y H
YH
Department of Biology, Texas Southern University, Houston, TX 77004, USA.
Florent
G
G
Hussain
T
T
Alkadhi
K A
KA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000241:Adenosine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D010726:Phosphodiesterase Inhibitors; D014667:Vasopressins; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000241:Adenosine