PROTECTION BY PHENTOLAMINE AGAINST THE EFFECTS OF PHENOXYBENZAMINE ON TRANSMITTER RELEASE ELICITED BY NERVE STIMULATION IN THE PERFUSED CAT HEART

British Journal of Pharmacology - Tập 52 Số 4 - Trang 549-557 - 1974
M Farah1, Salomón Z. Langer1
1Instituto de Investigeciones Farmacológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Junin 956-5° Piso, Buenos Aires, Argentina

Tóm tắt

The effects of cocaine, phentolamine and phenoxybenzamine on neuronal uptake of [3H]‐noradrenaline and on 3H‐transmitter and noradrenaline overflow elicited by nerve stimulation were determined in the perfused heart of the cat. During perfusion with cocaine 3.4 × 10−7m, there was a 2‐fold increase in transmitter overflow while neuronal uptake of [3H]‐noradrenaline was inhibited by 31.3 ± 2.1%. After exposure to phenoxybenzamine 8.7 × 10−7m for 20 min and washing with drug‐free solution for 165 min there was an 8‐fold increase in transmitter overflow during nerve stimulation. Under these conditions neuronal uptake of [3H]‐noradrenaline was inhibited by only 17.5 ± 5.4%. There was no significant change in transmitter overflow or in neuronal uptake of [3H]‐noradrenaline, 155 min after a 30 min exposure to phentolamine (3.2 × 10−5m). Perfusion with phentolamine (3.2 × 10−5m) before and during exposure to phenoxybenzamine (8.7 × 10−7m), prevented the increase in transmitter overflow observed after perfusion with phenoxybenzamine alone. Protection by phentolamine against the effects of phenoxybenzamine supports the view that the effects on transmitter release obtained after perfusion with phenoxybenzamine are due to the blockade of presynaptic α‐adrenoceptors which regulate transmitter release through a negative feed‐back mechanism.

Từ khóa


Tài liệu tham khảo

ADLER‐GRASCHINSKY E., 1972, Regulatión de la liberatión de noradrenalina por estímulo nervioso, Medicina, 32, 763

ADLER‐GRASCHINSKY E., 1974, Possible role of a β‐adrenoceptor in the regulation of noradrenaline release by nerve stimulation through a positive feed‐back mechanism, Br. J. Pharmac

ADLER‐GRASCHINSKY E., 1972, Metabolism of norepinephrine released by phenoxybenzamine in isolated guinea‐pig atria, J. Pharmac. exp. Ther., 180, 286

10.1016/0014-2999(68)90090-3

CUBEDDU L.X., 1974, The relationships between α‐receptor block, inhibition of norepinephrine uptake and the release and metabolism of 3H‐norepinephrine, J. Pharmac. exp. Ther., 188, 368

CUBEDDU L.X., 1974, Release of norepinephrine and dopamine‐beta‐hydroxylase by nerve stimulation. I. Role of neuronal and extraneuronal uptake and of alpha‐presynaptic receptors, J. Pharmac. exp. Ther., 190, 431

10.1113/jphysiol.1974.sp010495

10.1111/j.1476-5381.1972.tb07306.x

10.1111/j.1476-5381.1973.tb08367.x

FARAH M.B.&LANGER S.Z.(1972).Acción de los bloqueantes alfa sobre la liberación de noradrenalina por estímulo nervioso en al corazón perfundido de gato.IV Congreso Latinoamericano de Farmacología y Terapeútica p.81.

10.1111/j.1476-5381.1971.tb07160.x

10.1016/0006-2952(73)90231-1

10.1007/BF00246120

IVERSEN L.L., 1967, The Uptake and Storage of Noradrenaline in Sympathetic Nerves, 147

10.1111/j.1476-5381.1969.tb08501.x

KIRPEKAR S.M., 1971, Effect of flow‐stop on noradrenaline release from normal spleens treated with cocaine, phentolamine or phenoxybenzamine, Br. J. Pharmac., 43, 359, 10.1111/j.1476-5381.1971.tb08067.x

10.1016/0006-2952(74)90187-7

LANGER S.Z. ADLER E. ENERO M.A.&STEFANO F.J.E.(1971).The role of the alpha receptor in regulating noradrenaline overflow by nerve stimulation.XXVth. Int. Congr. Physiol. Sciences p.335.

10.1016/0003-2697(68)90316-3

SNEDECOR G.W., 1967, Statistical Methods

10.1007/BF00591535

10.1007/BF00505064

10.1007/BF00997091

10.1007/BF00998579

Thông tin
Thông tin xuất bản

British Journal of Pharmacology

Tập 52 Số 4

549-557

Thông tin tác giả