Inhibition of cyclic AMP production by alpha 2-adrenoceptor stimulation in the guinea-pig spinal cord slices.
In spinal cord slices isolated from guinea-pig and preincubated with 3H-adenine, 0.3-30 microM forskolin induced a dose-dependent increase in the content of 3H-cAMP, the maximal increase being about 8-fold. The selective alpha 2-adrenergic agonist UK-14,304 (10 microM) reduced both the basal and the forskolin stimulated levels of 3H-cAMP by 18-32%. Dose response curves of the effect of UK-14,304 on cAMP production in the spinal cord slices, stimulated with 3 microM forskolin, showed an IC50 of 37 nM and a maximally inhibitory effect of 27%. A number of other alpha 2-adrenergic agonist (clonidine, guanfacine, B-HT 920 and B-HT 933) also inhibited the forskolin stimulated 3H-cAMP production; clonidine and guanfacine being almost equipotent with UK-14,304, but their maximal inhibitory effects being only about 6-7%. B-HT 920 and B-HT 933 were less potent and their maximal inhibitory effects about 16-21%. The dose response curve of UK-14,304 on inhibition of forskolin stimulated cAMP production was shifted almost 50-fold to the right by 0.3 microM yohimbine. Prazosin (0.3 microM) did not affect the UK-14,304 dose response curve. It is concluded that alpha 2-adrenoceptor stimulation mediates inhibition of cAMP production in the guinea-pig spinal cord.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D011810:Quinoxalines; D005576:Colforsin; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D000242:Cyclic AMP; D011224:Prazosin