Inhibition of cAMP production by alpha 2-adrenoceptor stimulation in rabbit retina.
Adenylate cyclase activity in rabbit retinal homogenates can be stimulated directly by forskolin or through a receptor-mediated mechanism by vasoactive intestinal peptide (VIP). In contrast the alpha 2-adrenoceptor agonists clonidine and UK-14,304 reduce the basal cAMP level slightly. This was more evident following application of forskolin and VIP where the decrease of cAMP caused by clonidine and UK-14,304 is dose-dependent. The alpha 2-adrenoceptor agonist response is blocked by pertussis toxin and is insensitive to the phosphodiesterase inhibitor, isobutylmethylxanthine, suggesting the involvement of a Gi-protein. Clonidine and UK-14,304 attenuation of elevated cAMP levels can be inhibited by the alpha 2-receptor antagonist yohimbine and phentolamine but not by the specific alpha 1-receptor antagonist, prazosin. Serotonergic, cholinergic and beta-adrenergic receptor antagonists were without effect. The results demonstrate that alpha 2-adrenergic receptors in the retina exert inhibitory effects on adenylate cyclase activity mediated by an inhibitory guanine nucleotide regulating protein.
Osborne
N N
NN
Nuffield Laboratory of Ophthalmology, Oxford University, U.K.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D037342:Pertussis Toxin; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D000068438:Brimonidine Tartrate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D010727:Phosphoric Diester Hydrolases; D019204:GTP-Binding Proteins; D003000:Clonidine; D015056:1-Methyl-3-isobutylxanthine