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Potential involvement of a propranolol-insensitive atypical beta-adrenoceptor in the vasodilator effect of cyanopindolol in the human pulmonary artery

100%

Kozlowska H., Schlicker E., Kozlowski M., Baranowska M., Malinowska B.

Journal of Physiology and Pharmacology

2006

tom 57

nr 3

The aim of our study was to examine whether non ß1-/ß2-adrenoceptors participate in the relaxation of the human pulmonary artery. For this purpose the vasodilatory effect of the non-conventional partial ß-adrenoceptor agonist cyanopindolol was examined. Cyanopindolol (1 - 300 µM), studied in the presence of the ß1-/ß2-adrenoceptor antagonist propranolol, relaxed the human pulmonary artery preconstricted with serotonin 1 µM in a concentration-dependent manner (maximally by about 80%). This effect was diminished by bupranolol 10 µM (an antagonist of ß1-ß3-adrenoceptors and the low affinity state of the ß1-adrenoceptor) and CGP 20712 10 µM (known to antagonize the low-affinity state of the ß1-adrenoceptor at high concentrations). In further experiments, the effect of ß-adrenoceptor ligands on the serotonin-induced vasoconstriction was examined. The concentration-response curve for serotonin was not affected by cyanopindolol 30 µM, bupranolol 10 µM and CGP 20712 10 µM but shifted to the right by cyanopindolol 100 and 300 µM; the serotonin 5-HT2A receptor antagonist ketanserin 0.3 µM abolished the maximum contraction elicited by serotonin. In conclusion, the present study reveals that the vasodilatory effect of cyanopindolol in the human pulmonary artery consists of two components, i.e. activation of a propranolol-insensitive atypical ß-adrenoceptor and antagonism against 5-HT2A receptors.

Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors

86%

Zelaszczyk D., Kozlowska H., Baranowska U., Baranowska M., Reutelsterz A., Kiec-Kononowicz K., Malinowska B., Schlicker E.

Journal of Physiology and Pharmacology

2009

tom 60

nr 1

51-60

Bupranolol is an antagonist at the cardiostimulatory low-affinity state of ß1-adrenoceptors and we were interested whether this effect is shared by its fluorine (GD-6), methyl (DZ-51) and isopropyl analogue (DZ-13) and by the analogue hydroxylated at the tertiary butyl moiety (DZ-52). (-)-Bupranolol and compounds (-)-GD-6, (+)-GD-6, (-)-DZ-13, (+)-DZ-13, DZ-51 and DZ-52 antagonized the CGP 12177-induced tachycardia in pithed rats with “apparent pA2 values” of 6.1, 6.1, 4.6, 5.5, 4.6, 5.1 and 5.3, respectively. For comparison, their potencies and affinities at the high-affinity state of ß1-adrenoceptors were determined, using the xamoterol-induced tachycardia in pithed rats and [3H]CGP 12177 binding to rat cerebrocortical membranes. The respective “apparent pA2 values” in the functional experiments were 7.9, 8.1, 5.4, 8.4, 5.7, 7.3 and 6.8 and the pKi values in the binding experiments were 8.8, 8.4, 6.9, 8.5, 6.7, 8.4 and 8.2. In conclusion, (-)-bupranolol and its fluorine analogue (-)-GD-6 are equipotent at the low-affinity state of ß1-adrenoceptors. The stereoselectivity of GD-6 and DZ-13 suggests that the low-affinity state is indeed a receptor.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Baranowska M.

2 Kozlowska H.

2 Malinowska B.

2 Schlicker E.

1 Baranowska U.

1 Kiec-Kononowicz K.

1 Kozlowski M.

1 Reutelsterz A.

1 Zelaszczyk D.

1 2009

1 2006

Wyniki wyszukiwania

Potential involvement of a propranolol-insensitive atypical beta-adrenoceptor in the vasodilator effect of cyanopindolol in the human pulmonary artery

Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors