Expression of alpha-adrenoceptors in a human transformed lymphoblastoid cell line.
The presence of alpha-adrenergic receptors (absent in normal lymphocytes) has been demonstrated in transformed human lymphocytes of the Raji cell line. Binding properties of beta-adrenergic receptors were similar to those reported for normal lymphocytes. A single population of alpha 2-adrenergic receptors was characterized in intact Raji lymphoblasts by binding and saturation assays with the alpha 2-adrenergic antagonist yohimbine. Competition curves with [3H]yohimbine indicate the presence of typical alpha 2-adrenoceptors. Reaction of Raji with the alpha 2-adrenergic agonist clonidine (10(-6) M) stimulated their growth rate. In contrast, the alpha 1-adrenergic agonist methoxamine (10(-6) M) had no effect. Previous work indicates that Raji can actively produce thromboxanes (TX) and that these decreased atrium contractility. In agreement with these results and with the binding studies, it is now shown that clonidine stimulation enhanced the negative inotropic effects of Raji on isolated rat atria. This reaction was prevented by incubation of Raji with yohimbine (10(-6) M) but not with the alpha 1-adrenergic antagonist prazosin (10(-6) M) or the beta-adrenergic antagonist propranolol (10(-7) M). The biologic effect of Raji on rat atria was probably due to production of cyclooxygenase metabolites of arachidonic acid, because it was blocked by preincubation of the cells with the cyclooxygenase inhibitors indomethacin (10(-6) M) and aspirin (10(-4) M) or the thromboxane synthetase inhibitors nictindol (10(-5) M) and imidazole (10(-4) M).(ABSTRACT TRUNCATED AT 250 WORDS)
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Centro de Estudios Farmacológicos y de Principios Naturales (CEFAPRIN), CONICET, Buénos Aires, Argentina.
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008214:Lymphocytes / Q000737:chemistry*; D008297:Male; D009200:Myocardial Contraction; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine; D007213:Indomethacin