Influence of the alpha-adrenoreceptor naftopidil and doxazosin, on adrenaline-induced serotonin platelets: comparison with the antagonists, collagen and efflux by human effects of nifedipine.

Collagen (5 microg/ml) stimulation of washed platelets increased endogenous serotonin (5-HT) release to the medium from 13.88 1.39 to 188.67 26.37 pmol/108 platelets ( P < 0.001). Adrenaline (16 microM) also increased 5-HT release, from 11.0 1.46 to 110.6 29.9 pmol/108 platelets ( P < 0.02). Naftopidil enhanced collagen-induced 5-HT efflux; significant increases occurred with 2 microM (+71.6%, P < 0.01), 10 microM (+89.1%, P < 0.01) and 40 microM (+69.7%, P < 0.01). With 0.4 muM and 2 microM naftopidil, adrenaline-induced 5-HT release was enhanced, albeit non-significantly, whilst with 10 microM and 40 muM naftopidil release was reduced (40 microM,-58.5%, P < 0.05). Doxazosin increased collagen-induced 5-HT release, significant increases being recorded with 7.5 microM (+81.7%, P < 0.05) and 30 microM (+78.4%, P < 0.05). Adrenaline-induced 5-HT release was also increased by doxazosin, but not significantly. Collagen-stimulated 5-HT release was inhibited by nifedipine (7 microM,-38.8%, P < 0.05; 28 microM, -61.2%, P < 0.001). These data suggest that the-antagonists, naftopidil and doxazosin, and the Ca2+ channel blocker, nifedipine, influence agonist-induced platelet 5-HT release through different mechanisms. Thus naftopidil and doxazosin may possess 5-HT transporter-blocking activity. The observation that naftopidil inhibited, adrenaline-induced 5-HT release may indicate that naftopidil also inhibits adrenaline uptake and exchange with dense granular 5-HT, with consequent inhibition of 5-HT release and platelet aggregation. The data obtained with nifedipine are consistent with 5-HT release being reduced as a result of its inhibitory action on platelet Ca2+ mobilisation.

[1]  R. N. Brogden,et al.  Doxazosin , 1988, Drugs.

[2]  C. Smith.  Collagen stimulated release of serotonin by human platelets includes a sulphate conjugated component. , 1996, Platelets.

[3]  C. Smith,et al.  The potentiation of adrenaline-induced in vitro platelet aggregation by ADP, collagen and serotonin and its inhibition by naftopidil and doxazosin in normal human subjects. , 1995, British journal of clinical pharmacology.

[4]  D. Betteridge,et al.  Platelet transmembrane signalling responses to collagen in familial hypercholesterolaemia , 1994, European journal of clinical investigation.

[5]  G. Launay,et al.  Estimation of rate constants for serotonin uptake and compartmentation in normal human platelets. , 1994, The American journal of physiology.

[6]  M. Noble,et al.  Interaction between the effects of 5‐hydroxytryptamine and adrenaline on the growth of platelet thrombi in the coronary artery of the anaesthetized dog , 1993, British journal of pharmacology.

[7]  G. Rudnick,et al.  Non-neurotoxic amphetamine derivatives release serotonin through serotonin transporters. , 1993, Molecular pharmacology.

[8]  M. Lazzaro,et al.  5HT2-receptors and serotonin release: their role in human platelet aggregation. , 1993, Life sciences.

[9]  G. Rudnick,et al.  p-Chloroamphetamine induces serotonin release through serotonin transporters. , 1992, Biochemistry.

[10]  M. Condorelli,et al.  Divergent effects of serotonin on coronary-artery dimensions and blood flow in patients with coronary atherosclerosis and control patients. , 1991, The New England journal of medicine.

[11]  J. Storck,et al.  Urapidil inhibits 5-hydroxytryptamine induced platelet aggregation and 14C-5-hydroxytryptamine uptake in platelets. , 1990, Current medical research and opinion.

[12]  C. Smith,et al.  Serotonin: receptors and antagonists--summary of symposium. , 1990, Clinical physiology and biochemistry.

[13]  G. Tyce,et al.  Origin and Metabolism of Serotonin , 1990, Journal of cardiovascular pharmacology.

[14]  G. Blauw,et al.  Pathophysiological and pharmacotherapeutic aspects of serotonin and serotonergic drugs. , 1990, Clinical physiology and biochemistry.

[15]  J. Ieni,et al.  The 5-HT1A receptor probe [3H]8-OH-DPAT labels the 5-HT transporter in human platelets. , 1988, Life sciences.

[16]  F. De Clerck,et al.  Functional expression of the amplification reaction between serotonin and epinephrine on platelets. , 1988, Journal of cardiovascular pharmacology.

[17]  G. Rudnick.  ATP-driven H+ pumping into intracellular organelles. , 1986, Annual review of physiology.

[18]  H. Holmsen.  Platelet metabolism and activation. , 1985, Seminars in hematology.

[19]  P. Meyer,et al.  Decreased uptake of 3H-serotonin and endogenous content of serotonin in blood platelets in hypertensive patients. , 1984, Hypertension.

[20]  J. Wyllie,et al.  Loss of 5‐hydroxytryptamine from mammalian circulating labelled platelets , 1983, The Journal of physiology.

[21]  G. Picotti,et al.  CONTENT AND SUBCELLULAR LOCALIZATION OF CATECHOLAMINES AND 5‐HYDROXYTRYPTAMINE IN HUMAN AND ANIMAL BLOOD PLATELETS: MONOAMINE DISTRIBUTION BETWEEN PLATELETS AND PLASMA , 1979, British journal of pharmacology.

[22]  M. Scrutton,et al.  Novel α2-adrenoreceptors primarily responsible for inducing human platelet aggregation , 1979, Nature.

[23]  R. Feinman,et al.  Interrelations of platelet aggregation and secretion. , 1977, The Journal of clinical investigation.

[24]  H. Rosenkranz,et al.  Investigations on the Metabolism and Protein Binding of Nifedipine , 1975 .

[25]  J. Sneddon,et al.  Blood platelets as a model for monoamine-containing neurones. , 1973, Progress in neurobiology.

[26]  S. Bygdeman,et al.  Studies on the effect of adrenergic blocking drugs on catecholamine-induced platelet aggregation and uptake of noradrenaline and 5-hydroxytryptamine. , 1969, Acta physiologica Scandinavica.