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Titolo:
ACCELERATION BY CHRONIC TREATMENT WITH CLORGYLINE OF THE TURNOVER OF BRAIN ALPHA-2-ADRENOCEPTORS IN NORMOTENSIVE BUT NOT IN SPONTANEOUSLY HYPERTENSIVE RATS
Autore:
RIBAS C; MIRALLES A; GARCIASEVILLA JA;
Indirizzi:
UNIV ILLES BALEARS,DEPT BIOL FONAMENTAL & CIENCIES SALUT,NEUROFARMACOL LAB,CRA VALLDEMOSSA KM 75 E-07071 PALMA DE MALLORCA SPAIN UNIV ILLES BALEARS,DEPT BIOL FONAMENTAL & CIENCIES SALUT,NEUROFARMACOL LAB,CRA VALLDEMOSSA KM 75 E-07071 PALMA DE MALLORCA SPAIN
Titolo Testata:
British Journal of Pharmacology
fascicolo: 1, volume: 110, anno: 1993,
pagine: 99 - 106
SICI:
0007-1188(1993)110:1<99:ABCTWC>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
AGONIST-PROMOTED DESENSITIZATION; LONG-TERM TREATMENT; MUSCLE-CELL LINE; ADRENERGIC-RECEPTORS; NORADRENERGIC TRANSMISSION; MAJOR DEPRESSION; CEREBRAL-CORTEX; LIGAND-BINDING; DRUG-TREATMENT; INVIVO;
Keywords:
SPONTANEOUSLY HYPERTENSIVE RATS (SHR); BRAIN ALPHA-2-ADRENOCEPTORS; [H-3]-UK 14304; [H-3]-RX 821002; N-ETHOXYCARBONYL-2-ETHOXY-1,2-DIHYDROQUINOLINE (EEDQ); RECEPTOR TURNOVER; CLORGYLINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
C. Ribas et al., "ACCELERATION BY CHRONIC TREATMENT WITH CLORGYLINE OF THE TURNOVER OF BRAIN ALPHA-2-ADRENOCEPTORS IN NORMOTENSIVE BUT NOT IN SPONTANEOUSLY HYPERTENSIVE RATS", British Journal of Pharmacology, 110(1), 1993, pp. 99-106

Abstract

1 The aim of this study was to quantitate and compare the turnover ofalpha2-adrenoceptors in the cerebral cortex of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, and its modulation during chronic treatment with the monoamine oxidase (MAO) inhibitor,clorgyline. 2 In SHR, the specific binding of the agonist [H-3]-UK 14304 and of the antagonist [H-3]-RX 821002 was significantly reduced inthe brain (B(max) 15-19% lower) as compared to that in sex- and age-matched WKY rats. In contrast, no significant changes in the K(d) values for both radioligands were found between WKY and SHR rats. Therefore, SHR rats offer a genetic model with a lower density of alpha2-adrenoceptors in the brain. 3 Chronic treatment (21-35 days) with clorgyline(I mg kg-1, i.p.) markedly decreased the density of brain alpha2-adrenoceptors ([H-3]-UK 14304 binding) in Sprague-Dawley (B(max) reduced by 50%) and in WKY (B(max) reduced by 30%) rats without any apparent change in the affinity of the radioligand. In contrast, the density of brain alpha2-adrenoceptors in SHR was not down-regulated by chronic clorgyline treatment. 4 The recovery of [H-3]-UK 14304 binding after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 1.6 mg kg-1) (an alkylating agent for the alpha2-adrenoceptor) was assessed in control and clorgyline-treated (I mg kg-1; i.p. for 7-21 days) WKY and SHR rats to study the process of alpha2-adrenoceptor repopulation and to calculate receptor turnover parameters. 5 The simultaneous analysis of receptor recovery curves revealed that the turnover of brain alpha2-adrenoceptors in SHR rats was accelerated (k = 0.141 day-1; t1/2 = 4.9 days; r/k = 40 fmol mg-1 protein) compared to that in WKY rats (k = 0.085 day-1; t1/2 = 8.1 days; r/k = 54 fmol mg-1 protein) and that the reduced density of cortical alpha2-adrenoceptors(B(max) or r/k values) in SHR was probably due to an abnormal higher receptor degradation (DELTAk = 66%) and not to a decreased receptor synthesis which in fact showed a slight increase (DELTAr = 24%). 6 Treatment with clorgyline (I mg kg-1, i.p. for 21 days) accelerated the turnover of brain alpha2-adrenoceptors in WKY rats (k = 0.328 days-1; t1/2 = 2.1 days; r/k = 29 fmol mg-1 protein) and the greater increase in receptor degradation (DELTAk = 286%) over receptor synthesis (DELTAr =109%) led to down-regulation of receptor density (r/k = 46% lower). In contrast, treatment with clorgyline did not modify significantly theturnover of brain alpha2-adrenoceptors in SHR (k = 0. 192 days-1; t/2= 3.6 days; r/k = 39 fmol mg-1 protein), indicating that in this genetic model of hypertension, the desensitized alpha2-adrenoceptors cannot be further down-regulated by clorgyline treatment and that they lackthe expected adaptative increase in receptor synthesis.

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Documento generato il 29/11/20 alle ore 16:02:59