Dopamine-sensitive Adenylate Cyclase Activity in the Rat Caudate Nucleus during Exposure to Halothane and Enflurane

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Abstract

The effects of halothane and enflurane on the dopaminesensitive adenylate cyclase and cyclic 3',5'-adenosine monophosphate (cAMP)-phosphodiesterase in the homogenate of rat caudate nuclei were determined. Halothane, in concentrations of 2 and 5 vol per cent, increased adenylate cyclase activity by 16 (P < 0.005) and 26 (P < 0.001) per cent, respectively, above a mean basal value of 316.5 ± 8.8 pmol cAMP/mg protein/3 min. Enflurane, in concentrations of 3 and 5 vol per cent, increased adenylate cyclase activity by 11 (P < 0.05) and 22 (P < 0.02) per cent, respectively, above a mean basal value of 343.9 ± 10.4 pmol cAMP/mg protein/3 min. The activity of adenylate cyclase already stimulated by dopamine (even with the maximally-stimulating concentration) was further increased by both anesthetics, suggesting that the anesthetics and dopamine activate the enzyme at different sites. Haloperidol and droperidol, known dopamine receptor blockers, reversed the effect of halothane or enflurane on the adenylate cyclase. The antagonistic effect of haloperidol on anesthetic-induced adenylate cyclase activity is probably not related to its property to inhibit dopamine effect. Both Km forms of cAMP-phosphodiesterase were significantly depressed by halothane (3 vol per cent) and enflurane (5 vol per cent). The results suggest that an action of halothane and enflurane on the enzymes of the cAMP system, altering the response of the postsynaptic membrane to the transmitter substance, may be related to some of their effects on the process of chemical transmission.

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