Inhibition of cyclic AMP accumulation by alpha 2-adrenoceptors in the rat cerebral cortex.
The effects of alpha 2-adrenoceptor agonist and antagonists on the accumulation of cyclic AMP were examined in rat cerebral cortex slices. Norepinephrine (10(-4) M) caused a 123 +/- 11% increase in the cyclic AMP concentration in the cortical slices, which was greater than the increase (89 +/- 7% increase) caused by isoproterenol (10(-4) M) alone. However, the cyclic AMP response to norepinephrine was completely inhibited by propranolol (10(-4) M), a beta-adrenoceptor antagonist. Yohimbine (10(-7)-10(-5) M), an alpha 2-adrenoceptor antagonist, intensified the cyclic AMP response to norepinephrine by 30%, whereas, clonidine, an alpha 2-adrenoceptor agonist, decreased the response. Treatment with reserpine (3.0 mg/kg) reduced the density of [3H]p-aminoclonidine binding sites (Bmax, 93.8 +/- 18.4 fmol/mg protein) compared to the density in non-treated rats (154.4 +/- 33.5 fmol/mg protein). The potentiating effect of yohimbine and the inhibitory effect of clonidine on the cyclic AMP response to norepinephrine were also reduced. These results suggest that alpha 2-adrenoceptors regulate the accumulation of cyclic AMP in the rat cerebral cortex in an inhibitory fashion. The results also suggest that the accumulation is mediated through beta-adrenoceptors and that this response is intensified by alpha 1-adrenoceptor stimulation.
Kuno
N
N
Department of Clinical Pharmacology, Tottori University School of Medicine, Yonago, Japan.
Kamisaki
Y
Y
Itoh
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004347:Drug Interactions; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; C016986:apraclonidine; D012110:Reserpine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine