PROSTAGLANDINS AND HYPOTHALAMIC NEUROTRANSMITTER RECEPTORS INVOLVED IN HYPERTHERMIA - A CRITICAL-EVALUATION

The role of a prostaglandin of the E series (PGE) in the hypothalamic mechanisms underlying a fever continues to be controversial. This paper reviews the historical literature and current findings on the central action of the PGEs on body temperature (T-b). New experiments were undertaken to examine the local effect of muscarinic, nicotinic, serotonergic, alpha-adrenergic, or beta-adrenergic receptor antagonists at hypothalamic sites where PGE(1) caused a rise in T-b of the primate. Guide tubes for microinjection were implanted stereotaxically above sites in and around the anterior hypothalamic, preoptic area (AH/POA) of male Macaque monkeys. Following postoperative recovery, 30-100 ng of PGE(1) was micro-injected unilaterally in a volume of 1.0-1.5 mu l at sites in the AH/POA to evoke a rise in T-b, and once identified, pretreated with a receptor antagonist. PGE(1) hyperthermia was significantly reduced by microinjections of the muscarinic and nicotinic antagonists, atropine, or mecamylamine, at PGE(1) reactive sites in the AH/POA. The serotonergic antagonist, methysergide, injected at PGE(1) sensitive sites in the ventromedial hypothalamus also attenuated the rise in T-b. However, the 5-HT reuptake blocker, fluoxetine, and the beta-adrenergic receptor antagonist, propranolol, injected in the AH/POA failed to alter the PGE(1) hyperthermia. In contrast, the alpha-adrenergic antagonist, phentolamine, potentiated the increase in T-b at all PGE(1) reactive sites in the hypothalamus. An updated model is presented to explain how the concurrent actions of aminergic neurotransmitters acting on their respective receptors in the hypothalamus can interact with a PGE to elicit hyperthermia. Finally, an evaluation of the current literature including recent findings on macrophage inflammatory protein (MIP-1) supports the conclusion that a PGE in the brain is neither an obligatory nor essential factor for the expression of a pyrogen fever.