Central effects of dibutyryl cyclic AMP and GMP on the temperature in conscious rabbits

Abstract

Intracerebroventricular (i.c.v.) administration of dibutyryl cyclic AMP (Db-cAMP)- and dibutyryl cyclic GMP (Db-cGMP)-induced hyperthermia in rabbits. Central administration of 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK 62711), a selective inhibitor of cAMP phosphodiesterase, only accentuated the hyperthermia due to Db-cAMP whereas a selective inhibitor of cGMP phosphodiesterase, 2-O-proproxyphenyl-8-azapurin-6-one (M and B 22948), only potentiated the hyperthermia caused by Db-cGMP. The hyperthermia due to Db-cAMP and Db-cGMP was not mediated through prostaglandins (PG). In contrast, central administration of an α-adrenergic receptor antagonist, phenoxybenzamine, or a β-adrenergic receptor antagonist, sotalol, only attenuated the hyperthermic response to Db-cAMP while a cholinergic muscarinic receptor antagonist, atropine, specifically antagonized Db-cGMP-induced hyperthermia. I.c.v. administration of a protein synthesis inhibitor, anisomycin, did inhibit the hyperthermia due to Db-cAMP and Db-cGMP. Opiate antagonist, naloxone, did not antagonize Db-cAMP- nd Db-cGMP-induced hyperthermia. These results suggest that a protein mediator is implicated in the induction of hyperthermia by Db-cAMP and Db-cGMP and that cAMP and cGMP may be involved through α/β-adrenergic and cholinergic muscarinic receptors respectively in the central regulation of heat production/conservation in rabbits.