Preoptic 1- and 2-noradrenergic agonists induce, respectively, PGE2- independent and PGE2-dependent hyperthermic responses in guinea pigs

Feleder, Carlos, Vit Perlik, and Clark M. Blatteis. Preoptic 1and 2-noradrenergic agonists induce, respectively, PGE2-independent and PGE2-dependent hyperthermic responses in guinea pigs. Am J Physiol Regul Integr Comp Physiol 286: R1156–R1166, 2004. First published February 12, 2004; 10.1152/ajpregu.00486.2003.— We have shown previously that norepinephrine (NE) microdialyzed into the preoptic area (POA) of conscious guinea pigs stimulates local PGE2 release. To identify the cyclooxygenase (COX) isozyme that catalyzes the production of this PGE2 and the adrenoceptor (AR) subtype that mediates this effect, we microdialyzed for 6 h NE, cirazoline ( 1-AR agonist), and clonidine ( 2-AR agonist) into the POA of conscious guinea pigs pretreated intrapreoptically (intraPOA) with SC-560 (COX-1 inhibitor) or nimesulide or MK-0663 (COX-2 inhibitors) and measured the animals’ core temperature (Tc) and intra-POA PGE2 responses. Cirazoline induced Tc rises promptly after the onset of its dialysis without altering PGE2 levels. NE and clonidine caused early falls followed by late rises of Tc; intra-POA PGE2 levels were closely correlated with this thermal course. COX-1 inhibition attenuated the clonidine-induced Tc and PGE2 falls but not the NE-elicited hyperthermia, but COX-2 inhibition suppressed both the clonidineand NE-induced Tc and PGE2 rises. Coinfused cirazoline and clonidine reproduced the late Tc rise of clonidine but not its early fall and also not the early rise produced by cirazoline; on the other hand, the PGE2 responses were similar to those to NE. Prazosin ( 1-AR antagonist) and yohimbine ( 2-AR antagonist) blocked the effects of their respective agonists. These results indicate that 1and 2-AR agonists microdialyzed into the POA of conscious guinea pigs evoke distinct Tc responses: 1-AR activation produces quick, PGE2independent Tc rises, and 2-AR stimulation causes an early Tc fall and a late, COX-2/PGE2-dependent Tc rise.