Adenosine regulation of cyclic 3',5'-adenosine monophosphate formation in rat spinal cord.
Adenosine stimulates the formation of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in rat spinal cord tissue slices in a concentration-dependent manner with maximal accumulation (30 pmol/mg of protein) at a concentration of 1 mM (Ec50 50 microM). 2-Chloroadenosine (EC50 1 microM) produced a maximal accumulation to 50 pmol/mg of protein. The adenosine antagonists, theophylline and isobutylmethylxanthine, block the increase, and the phosphodiesterase inhibitor, RO 20-1724, potentiates the increase in cyclic AMP accumulation. Adenosine deaminase eliminated the adenosine-dependent increase. Cyclic AMP accumulation was also enhanced by ATP, ADP and 5'-AMP. However, the stimulation due to these nucleotides was dependent upon conversion to adenosine. The increase in cyclic AMP accumulation was more than additive when adenosine was combined with norepinephrine. This potentiation effect is blocked by theophylline, isobutylmethylxanthine and alpha adrenergic antagonists. Additional experiments revealed that only postsynaptic alpha adrenergic agonists were capable of potentiating the response to adenosine. The interaction is concentration-dependent, is also observed with phosphorylated nucleotides of adenosine and is blocked specifically by alpha receptor antagonists. Receptor binding assays revealed that adenosine does not alter the number of alpha adrenergic receptors. Both the alpha receptor and adenosine-stimulated cyclic AMP accumulation were Ca++-dependent. These results suggest that adenosine-dependent cyclic AMP formation in rat spinal cord is mediated through two types of receptors, one of which is independent, and the other coupled to the alpha adrenergic receptor.
D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium