Prostaglandin E(2) fever mediated by inhibition of the GABAergic transmission in the region immediately adjacent to the organum vasculosum of the lamina terminalis.
Unilateral microinjection of prostaglandin (PG)E(2) into a region immediately adjacent to the organum vasculosum of the lamina terminalis (peri-OVLT) in the preoptic area elicited thermogenic, tachycardic, cutaneous vasoconstrictive, and hyperthermic responses simultaneously in urethane-chloralose-anesthetized rats. The magnitude of these responses increased dose-dependently over the range of 57 fmol-2.8 pmol, except for the vasoconstrictive response. Microinjection of a GABA(A) receptor antagonist, bicuculline methiodide or gabazine (5-20 pmol), into the PGE(2)-sensitive site in the peri-OVLT region also elicited responses similar to those induced by PGE(2). Although administration of a GABA(A) receptor agonist, muscimol (10 pmol), microinjected into the same site alone usually had no effect on the rate of whole-body O(2) consumption, heart rate or colon and skin temperatures, all PGE(2)-induced responses were blocked 10 min after the muscimol pretreatment and recovered at 50-90 min. Pretreatment with the vehicle, saline, had no effect on the PGE(2)-induced responses. These results suggest that spontaneous release of GABA and tonic activation of GABA(A) receptors in the peri-OVLT region prevent the elevation in the body core temperature under normal circumstances and that PGE(2)-induced febrile responses are mediated, at least in part, by inhibition of the GABAergic transmission in this area.
Osaka
Toshimasa
T
National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku, 162-8636, Tokyo, Japan. osaka@nih.go.jp
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced*; D018756:GABA Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007031:Hypothalamus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011301:Preoptic Area / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D011724:Pyridazines; D009118:Muscimol; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D015232:Dinoprostone; D001640:Bicuculline