Influence of eicosanoids on serotonin release in the rat brain: inhibition by prostaglandins E1 and E2 |
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| Authors: | Eberhard Schlicker Klaus Fink Manfred Göthert |
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| Institution: | (1) Department of Pharmacology, Welsh School of Pharmacy, University of Wales, Institute of Science and Technology, PO Box 13, CFI 3XF Cardiff;(2) Department of Cardiology, University of Wales, College of Medicine, C174 4XN Cardiff, UK;(3) Present address: Department of Pharmacology and Therapeutics, University of Liverpool, L9 3BX Liverpool, UK;(4) Present address: Division of Pharmacology and Toxicology Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada;(5) Present address: Department of Cardiology, St. Mary's Medical School, London |
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| Abstract: | Summary Cardiac alpha- and beta-adrenoceptor sensitivities were examined after chronic pretreatment of rats with reserpine. Increases in sensitivity would indicate that the receptor is under the influence of the sympathetic innervation, removal by catecholamine depletion with reserpine of the tonic effect of neurotransmitter release would permit receptor upregulation. The positive inotropic responses of paced left atria and papillary muscles and the positive chronotropic responses of spontaneously beating right atria were recorded. A concentration-response curve to isoprenaline (beta-adrenoceptor-mediated) was followed, in the presence of beta-blockade, by one to methoxamine (alpha-adrenoceptor-mediated). Methoxamine exerted positive inotropy of left atria and papillary muscles, the maxima being 43.2 ± 2.7 and 26.8 ± 4.4% of the isoprenaline maxima. A small positive chronotropy (16.5 ± 5.6% maximum) of right atria occurred. After pretreatment with reserpine (1.0 mg kg–1 i.p. daily) for 7 days, the three preparations displayed supersensitivity to isoprenaline, revealed as a significant displacement (P < 0.05) of the concentration-response curves to the left of those for control rats. Reserpine pretreatment, however, had no effect on the sensitivity to methoxamine. The increase in beta-adrenoceptor sensitivity to isoprenaline after reserpine pretreatment was accompanied by a significant 41.3% increase (P < 0.05) in the number of 3H]-dihydroalprenolol (3H]-DHA) binding sites (B
max) in ventricular membranes, although the dissociation constant (K
D) was unaffected. There were more alpha-adrenoceptor 3H]-prazosin binding sites in ventricular than atrial membranes. However, there was no difference in K
D or B
max between reserpine-pretreated and control tissues. It is proposed that the increase in beta-adrenoceptor sensitivity and binding sites arises from the depletion-induced loss of neuronal noradrenaline release onto the beta-adrenoceptors which are therefore directly under the influence of the neurotransmitter. The failure of cardiac alpha-adrenoceptors to exhibit supersensitivity and increased numbers suggests that they are not directly affected by the sympathetic innervation.
Send offprint requests to K. J. Broadley at the above address |
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| Keywords: | Alpha- and beta-adrenoceptor sensitivity Reserpine [3H]-dihydroalprenolol binding [3H]Prazosin binding Positive inotropy and chronotropy |
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