EFFECTS OF ALPHA-ADRENOCEPTOR ANTAGONISTS ON CONTRACTILE RESPONSES TO 5-HYDROXYTRYPTAMINE IN DOG SAPHENOUS-VEIN

被引:50
作者
HUMPHREY, PPA
机构
[1] Department of Pharmacology, Allen & Hanburys Research Ltd., Ware, Hertfordshire
关键词
D O I
10.1111/j.1476-5381.1978.tb17281.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
5‐Hydroxytryptamine (5‐HT) contracted isolated saphenous vein strips of the dog, producing a biphasic concentration‐effect curve. The first phase occurred with low concentrations of 5‐HT (1.0 × 10−8 to 5.0 × 10−6mol/1) with a plateau between 1.0 × 10−6mol/1 and 1.0 × 10−5mol/1. The second phase occurred with high concentrations of 5‐HT (greater than 1.0 × 10−5 mol/1). The α‐adrenoceptor antagonists, phentolamine (5.0 × 10−8 to 5.0 × 10−7 mol/1), labetalol (1.0 × 10−6 to 1.0 × 10−5 mol/1) and thymoxamine (1.0 × 10−6 to 1.0 × 10−5 mol/1), antagonized responses to high concentrations of 5‐HT but responses to low concentrations of 5‐HT were not antagonized. The effects of high concentrations of 5‐HT were antagonized by cocaine (1.0 × 10−6 to 1.0 × 10−5 mol/1) and were not evident in veins removed from dogs pretreated with syrosingopine. It is concluded that in the saphenous vein, low concentrations of 5‐HT act directly on specific 5‐HT receptors and that high concentrations of 5‐HT also act indirectly on α‐adrenoceptors by displacing noradrenaline from neuronal stores. 1978 British Pharmacological Society
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页码:671 / 675
页数:5
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  • [1] Apperley, Humphrey P.P.A., Levy G.P., Receptors for 5‐hydroxytryptamine and noradrenaline in rabbit isolated ear artery and aorta, Br. J. Pharmac., 58, pp. 211-221, (1976)
  • [2] Apperley, Humphrey P.P.A., Levy G.P., Two types of excitatory receptor for 5‐hydroxytryptamine in dog vasculature?, Br. Pharmac., 61, (1977)
  • [3] Brandao F., A comparative study of the role played by some inactivation pathways in the disposition of the transmitter in the rabbit aorta and the saphenous vein of the dog, Blood Vesels, 13, pp. 309-318, (1976)
  • [4] Carrier O., Holland W.C., Supersensitivity in perfused isolated arteries after reserpine, J. Pharmac. exp. Ther., 149, pp. 212-218, (1965)
  • [5] Edvinnson L., Hardebo J.E., Characterisation of serotonin receptors in intracranial and extracranial vessels, Acta Physiologica Scandinavica, 97, pp. 523-525, (1976)
  • [6] Feniuk W., Humphrey P.P.A., Levy G.P., Further evidence for two types of excitatory receptor for 5‐hydroxytryptamine in dog vasculature, Br. J. Pharmac., 61, (1977)
  • [7] Fozard J.R., Comparative effects of four migraine prophylactic drugs on an isolated extracranial artery, Eur. J. Pharmac., 6, pp. 127-139, (1976)
  • [8] Fozard J.R., Mwaluko G.M.P., Mechanism of the indirect symphathomimetic effect of 5‐hydroxytryptamine on the isolated heart of the rabbit, Br. J. Pharmac., 57, pp. 115-125, (1976)
  • [9] Gaddum J.H., Theories of drug antagonism, Pharmac. Rev., 9, pp. 211-218, (1957)
  • [10] Gillis C.N., Characteristics of norepinephrine retention by a subcellular fraction of rabbit heart, J. Pharmac exp. Ther., 146, pp. 54-60, (1964)