title: Potentiated modulation of pregnolone on GABAA receptors in behaviorally stressed borderline-hypertensive rats.
abstract: The modulatory effects of behavioral stress on [(3)H]flunitrazepam, an agonist for the central-type benzodiazepine receptor binding to the GABA(A)-benzodiazepine receptor complex, in borderline hypertensive rats (BHR) were examined. In repeatedly immobilized (for 2 weeks, for 2 h/d) BHR, enhancement of [(3)H]flunitrazepam binding to the receptor was observed to be potentiated. The percent enhancement of [(3)H]flunitrazepam binding in BHR was higher than that in normotensive control Wistar-Kyoto rats. Pregnanolone, a neuroactive steroid that has been reported to be a putative endogenous modulator in the stress response, concentration dependently enhanced [(3)H]flunitrazepam binding to the receptor. Enhancement of [(3)H]flunitrazepam binding was observed to be potentiated by the same immobilized stress, and the EC(50) values of pregnanolone in BHR was significantly lower than those in controls and E(max) values were higher. From the above results, it can be concluded that neural modulation to behavioral stress, especially in GABAergic neurotransmission, is exaggerated in BHR. We propose strain-specific differences of stress reactivity as an important pathogenetic factor in psychosomatic disorders including stress-induced hypertension. This is supported by reports showing exaggerated cardiovascular and symathoadrenal responses to stress in BHR.
authors.affiliation: Department of Pharmacology, College of Medicine, Yeungnam University, Taegu 705-717, Republic of Korea.
authors.forename: Hyoung Chul
authors.initials: HC
authors.lastname: Choi
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Jong-Bum
authors.initials: JB
authors.lastname: Lee
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Park
authors.forename: Jae-Tae
authors.initials: JT
authors.lastname: Lee
authors.forename: Hun-Gu
authors.initials: HG
authors.lastname: Kang
authors.forename: Byung-Jo
authors.initials: BJ
authors.lastname: Kang
authors.forename: Kwang Youn
authors.initials: KY
authors.lastname: Lee
authors.forename: Jeoung-Hee
authors.initials: JH
authors.lastname: Ha
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D011963:Receptors, GABA-A / Q000187:drug effects*; D012149:Restraint, Physical; D013045:Species Specificity; D013315:Stress, Psychological / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018757:GABA Modulators; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D011280:Pregnanolone