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.