Inhibition of Cyclic AMP Production by α2‐Adrenoceptor Stimulation in the Guinea‐Pig Spinal Cord Slices

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Abstract
In spinal cord slices isolated from guinea-pig and preincubated with 3H-adenine, 0.3–30 μM forskolin induced a dose-dependent increase in the content of 3H-cAMP, the maximal increase being about 8-fold. The selective α2-adrenergic agonist UK-14,304 (10 μM) 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 μM forskolin, showed an IC50 of 37 nM and a maximally inhibitory effect of 27%. A number of other α2-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 μM yohimbine. Prazosin (0.3 μM) did not affect the UK-14,304 dose resonse curve. It is concluded that α2-adrenoceptor stimulation mediates inhibition of cAMP production in the guinea-pig spinal cord.
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