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Titolo:
Second messengers in platelet aggregation evoked by serotonin and A23187, a calcium ionophore
Autore:
Connor, JD; Rasheed, H; Gilani, AH; Cheema, M; Rizvi, Z; Saeed, SA;
Indirizzi:
Aga Khan Univ, Dept Biol & Biomed Sci, Karachi 74800, Pakistan Aga Khan Univ Karachi Pakistan 74800 Biomed Sci, Karachi 74800, Pakistan
Titolo Testata:
LIFE SCIENCES
fascicolo: 23, volume: 69, anno: 2001,
pagine: 2759 - 2764
SICI:
0024-3205(20011026)69:23<2759:SMIPAE>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; CYCLOOXYGENASE PATHWAYS; SYNERGISTIC INTERACTION; BLOOD-PLATELETS; RECEPTOR-SITES; CA2+ CHANNELS; INHIBITION; ACTIVATION; ANTAGONISTS; ADRENALINE;
Keywords:
calcium ionophore-A23187; 5-hydroxytryptamine; phospholipase C; platelet aggregation; wortmannin; phosphatidylinositide 3-kinase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Saeed, SA Aga Khan Univ, Dept Biol & Biomed Sci, POB 3500, Karachi 74800, Pakistan Aga Khan Univ POB 3500 Karachi Pakistan 74800 i 74800, Pakistan
Citazione:
J.D. Connor et al., "Second messengers in platelet aggregation evoked by serotonin and A23187, a calcium ionophore", LIFE SCI, 69(23), 2001, pp. 2759-2764

Abstract

We investigated the combined effect of 5-hydroxytryptamine (5-HT, serotonin) and calcium ionophore (A23187) on human platelet aggregation. Aggregation, monitored at 37 degreesC using a Dual-channel Lumi-aggregometer, was recorded for 5 min after challenge by a change in light transmission as a function of time. 5-HT (2-200 muM) alone did not cause platelet aggregation, but markedly potentiated A23187 (low dose) induced aggregation. Inhibitory concentration (IC50) values for a number of compounds were calculated as means SEM from dose-response determinations. Synergism between 5-HT (2-5 muM) and A23187 (0.5-2 muM) was inhibited by 5-HT receptor blockers, methysergide(IC50 = 18 muM) and cyproheptadine (IC50 = 20 muM), and calcium channel blockers (verapamil and diltiazem, IC50 = 20 muM and 40 muM respectively). Interpretation of the effects of these blockers is complicated by their lack of specificity. Similarly, U73122, an inhibitor of phospholipase C (PLC), blocked the synergistic effect at an IC50 value of 9.2 muM. Wortmannin, a phosphatidylinositide 3-kinase (PI 3-K) inhibitor, also blocked the response (IC50 = 2.6 muM). However, neither genistein, a tyrosine-specific protein kinase inhibitor, nor chelerythrine, a protein kinase C inhibitor, affected aggregation at concentrations up to 10 muM. We conclude that the synergistic interaction between 5-HT and ionophore may be mediated by activation of PLC/Ca2+ and PI 3-kinase signalling pathways, but definitive proof will require other enzyme inhibitors with greater specificity. (C) 2001 Elsevier Science Inc. Ali rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 06:51:32