Alpha adrenergic receptor mediated formation of cyclic AMP in rat spinal cord.
Methoxamine and phenylephrine (PE), postsynaptic alpha adrenergic agonists stimulated the accumulation of cyclic AMP in spinal cord tissue slices. Naphazoline, oxymetazoline and clonidine, previously shown to have greater efficacy at presynaptic alpha receptors did not alter accumulation and, in fact, blocked the PE response. The PE-stimulation was completely inhibited by postsynaptic alpha antagonists, incompletely by agents which bl ock presynaptic alpha receptors, and slightly by the beta blocker propranolol. Pe-stimulated accumulation was potentiated by phosphodiesterase inhibition (RO 20-1724). In contrast to previous reports on the requirement of the copresence of adenosine for alpha receptor stimulated accumulation of cyclic AMP in neuronal tissue, the PE-stimulation in spinal cord slices was unchanged by adenosine receptor blockade (theophylline), hydrolysis of endogenous adenosine (adenosine deaminase), inhibition of adenosine deaminase (EHNA) or blockade of adenosine uptake (dipyridamole). Added adenosine increased basal accumulation and produced a marked potentiation of the PE response. From this data it is evident that, in spinal cord tissue slices, there occurs a postsynaptic alpha adrenergic receptor linked to cyclic AMP accumulation which does not require the presence of other neurohumoral agents for activation.
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D009278:Naphazoline / Q000494:pharmacology; D010109:Oxymetazoline / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D010656:Phenylephrine; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D010109:Oxymetazoline; D000242:Cyclic AMP; D009278:Naphazoline; D008729:Methoxamine; D003000:Clonidine