Preoptic α1- and α2-noradrenergic agonists induce, respectively, PGE2-independent and PGE2-dependent hyperthermic responses in guinea pigs

Abstract

We have shown previously that norepinephrine (NE) microdialyzed into the preoptic area (POA) of conscious guinea pigs stimulates local PGE2release. To identify the cyclooxygenase (COX) isozyme that catalyzes the production of this PGE2and the adrenoceptor (AR) subtype that mediates this effect, we microdialyzed for 6 h NE, cirazoline (α1-AR agonist), and clonidine (α2-AR agonist) into the POA of conscious guinea pigs pretreated intrapreoptically (intra-POA) with SC-560 (COX-1 inhibitor) or nimesulide or MK-0663 (COX-2 inhibitors) and measured the animals' core temperature (Tc) and intra-POA PGE2responses. Cirazoline induced Tcrises promptly after the onset of its dialysis without altering PGE2levels. NE and clonidine caused early falls followed by late rises of Tc; intra-POA PGE2levels were closely correlated with this thermal course. COX-1 inhibition attenuated the clonidine-induced Tcand PGE2falls but not the NE-elicited hyperthermia, but COX-2 inhibition suppressed both the clonidine- and NE-induced Tcand PGE2rises. Coinfused cirazoline and clonidine reproduced the late Tcrise of clonidine but not its early fall and also not the early rise produced by cirazoline; on the other hand, the PGE2responses were similar to those to NE. Prazosin (α1-AR antagonist) and yohimbine (α2-AR antagonist) blocked the effects of their respective agonists. These results indicate that α1- and α2-AR agonists microdialyzed into the POA of conscious guinea pigs evoke distinct Tcresponses: α1-AR activation produces quick, PGE2-independent Tcrises, and α2-AR stimulation causes an early Tcfall and a late, COX-2/PGE2-dependent Tcrise.