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Titolo:
Activation of the alpha(2A)-adrenoceptor mediates deceleration of the deaggregation component of the response to ADP or 5-HT in human platelets in vitro
Autore:
Maayani, S; Schwarz, T; Craddock-Royal, B; Tagliente, TM;
Indirizzi:
CUNY Mt Sinai Sch Med, Dept Anesthesiol, Basic Res Lab, New York, NY 10029USA CUNY Mt Sinai Sch Med New York NY USA 10029 es Lab, New York, NY 10029USA
Titolo Testata:
PLATELETS
fascicolo: 6, volume: 12, anno: 2001,
pagine: 359 - 375
SICI:
0953-7104(200109)12:6<359:AOTAMD>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALPHA-ADRENERGIC RECEPTORS; CANINE CORONARY-ARTERIES; CYCLIC FLOW VARIATIONS; HUMAN-BLOOD PLATELETS; ALPHA-2-ADRENERGIC RECEPTOR; ADENYLATE-CYCLASE; MORNING INCREASE; P2Y(1) RECEPTOR; PHOSPHOINOSITIDE 3-KINASE; MICROPLATE READER;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
107
Recensione:
Indirizzi per estratti:
Indirizzo: Maayani, S CUNY Mt Sinai Sch Med, Dept Anesthesiol, Basic Res Lab, Box 1010,1 GustaveL Levy Pl, New York, NY 10029 USA CUNY Mt Sinai Sch Med Box 1010,1 Gustave L Levy Pl New York NY USA 10029
Citazione:
S. Maayani et al., "Activation of the alpha(2A)-adrenoceptor mediates deceleration of the deaggregation component of the response to ADP or 5-HT in human platelets in vitro", PLATELETS, 12(6), 2001, pp. 359-375

Abstract

Platelet aggregation requires the concomitant activation of at least one G(i)- and one G(q)-coupled receptor. Epinephrine (EPI) amplifies the response elicited by a number of agonists for platelet aggregation. This study tested the hypothesis that platelet alpha (2A)-adrenoceptor activation causes deceleration of the deaggregation component of the platelet aggregation response when activated concomitantly with the G(q)-coupled adenosine diphosphate (ADP) P2Y(1) or 5-hydroxytryptamine(2A) receptor. The time course of the aggregation response of human platelet-rich plasma following activation of combinations of two or three receptors was assessed by turbidometry usinglepirudin anticoagulation. Simultaneous activation of specific two- and three-receptor combinations was achieved using selective antagonists for the P2Y(12) and P2Y(1) receptor subtypes. Steady-state and kinetic parameters, obtained using a four-compartment kinetic model, were used to assess the effects on the net aggregation response. Graded alpha (2A)-adrenoceptor activation was associated with a concentration-dependent decrease of the rate constant of deaggregation. Activation of both ADP receptor subtypes and the alpha (2A)-adrenoceptor produced a concentration-dependent, mutual amplification of the aggregation response. In addition, when three receptors were simultaneously activated, mutual amplification of the aggregation response was observed at physiologically relevant concentrations of epinephrine or norepinephrine (NE) and ADP. We propose that similar to the P2Y12 receptor, activation of the alpha (2A)-adrenoceptor decelerates the deaggregation component shifting the balance toward increased net aggregation. The effects of EPI and NE on the aggregation response may contribute to the mechanism of increased thrombotic risk present in certain pathophysiological and disease states.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 11:45:08