Potentiated modulation of pregnolone on GABAA receptors in behaviorally stressed borderline-hypertensive rats.
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.
Choi
Hyoung Chul
HC
Department of Pharmacology, College of Medicine, Yeungnam University, Taegu 705-717, Republic of Korea.
Kim
Jong-Yeon
JY
Lee
Jong-Bum
JB
Park
Yong-Hoon
YH
Lee
Jae-Tae
JT
Kang
Hun-Gu
HG
Kang
Byung-Jo
BJ
Lee
Kwang Youn
KY
Ha
Jeoung-Hee
JH
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
D018757:GABA Modulators; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D011280:Pregnanolone