Abstract
1. The technique of microelectrophoresis was used to compare the actions of a range of adrenoceptor agonists on single cortical neurones in the rat anaesthetized with halothane. 2. Phenylephrine and methoxamine were exclusively excitatory, whereas salbutamol was entirely depressant. Noradrenaline and isoprenaline could evoke both excitatory and depressant responses. Lower doses of isoprenaline usually evoked depressions, whereas higher doses, on the same cell, evoked excitatory responses. 3. The alpha-adrenoceptor blocking agents, phentolamine and phenoxybenzamine, reversibly antagonized excitatory responses to adrenoceptor agonists, without affecting depressant responses to adrenoceptor agonists or excitatory responses to acetylcholine. 4. The beta-adrenoceptor blocking agents, propranolol and sotalol, reversibly antagonized both depressant and excitatory responses to adrenoceptor agonists, without affecting responses to acetylcholine. When the effect of sotalol on excitatory and depressant responses to adrenoceptor agonists was compared on the same cell, the depressant responses could be selectively antagonized, without affecting the excitatory responses. 5. It is concluded that (a) responses of cortical neurones to adrenoceptor agonists are mediated by both alpha- and beta-receptors; (b) these alpha- and beta-receptors give rise to opposite effects: the alpha-receptors being excitatory and the beta-receptors being inhibitory; and (c) responses of many neurones reflect the presence of both types of receptor.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Besse J. C., Furchgott R. F. Dissociation constants and relative efficacies of agonists acting on alpha adrenergic receptors in rabbit aorta. J Pharmacol Exp Ther. 1976 Apr;197(1):66–78. [PubMed] [Google Scholar]
- Bevan P., Bradshaw C. M., Roberts M. H., Szabadi E. The effect of microelectrophoretically applied mescaline on cortical neurones. Neuropharmacology. 1974 Nov;13(10-11):1033–1045. doi: 10.1016/0028-3908(74)90094-x. [DOI] [PubMed] [Google Scholar]
- Bevan P., Bradshaw C. M., Szabadi E. Neuronal responses to adrenoceptor agonists in the cerebral cortex: evidence for excitatory alpha-adrenoceptors and inhibitory beta-adrenoceptors [proceedings]. Br J Pharmacol. 1976 Nov;58(3):418P–418P. [PMC free article] [PubMed] [Google Scholar]
- Bevan P., Bradshaw C. M., Szabadi E. Proceedings: Potentiation and antagonism of neuronal responses to monoamines by methysergide and sotalol. Br J Pharmacol. 1974 Mar;50(3):445P–445P. [PMC free article] [PubMed] [Google Scholar]
- Bevan P., Bradshaw C. M., Szabadi E. The action of microelectrophoretically applied L-3,4-dihydroxyphenylalanine (DOPA) on single cortical neurones. Br J Pharmacol. 1976 Oct;58(2):239–245. doi: 10.1111/j.1476-5381.1976.tb10401.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradshaw C. M., Roberts M. H., Szabadi E. Kinetics of the release of noradrenaline from micropipettes: interaction between ejecting and retaining currents. Br J Pharmacol. 1973 Dec;49(4):667–677. doi: 10.1111/j.1476-5381.1973.tb08543.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradshaw C. M., Szabadi E., Roberts M. H. The reflection of ejecting and retaining currents in the time-course of neuronal responses to microelectrophoretically applied drugs. J Pharm Pharmacol. 1973 Jul;25(7):513–520. doi: 10.1111/j.2042-7158.1973.tb09150.x. [DOI] [PubMed] [Google Scholar]
- Brittain R. T., Jack D., Ritchie A. C. Recent beta-adrenoreceptor stimulants. Adv Drug Res. 1970;5:197–253. [PubMed] [Google Scholar]
- Furchgott R. F. Pharmacological characteristics of adrenergic receptors. Fed Proc. 1970 Jul-Aug;29(4):1352–1361. [PubMed] [Google Scholar]
- Johnson E. S., Roberts M. H., Sobieszek A., Straughan D. W. Noradrenaline sensitive cells in cat cerebral cortex. Int J Neuropharmacol. 1969 Dec;8(6):549–566. doi: 10.1016/0028-3908(69)90072-0. [DOI] [PubMed] [Google Scholar]
- KRNJEVIC K., PHILLIS J. W. Actions of certain amines on cerebral cortical neurones. Br J Pharmacol Chemother. 1963 Jun;20:471–490. doi: 10.1111/j.1476-5381.1963.tb01484.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nickerson M. New developments in adrenergic blocking drugs. Ann N Y Acad Sci. 1967 Feb 10;139(3):571–579. doi: 10.1111/j.1749-6632.1967.tb41230.x. [DOI] [PubMed] [Google Scholar]
- Patil P. N., Tye A., May C., Hetey S., Miyagi S. Steric aspects of adrenergic drugs. XI. Interactions of dibenamine and beta adrenergic blockers. J Pharmacol Exp Ther. 1968 Oct;163(2):309–319. [PubMed] [Google Scholar]
- Schümann H. J., Endoh M. alpha-Adrenoceptors in the ventricular myocardium: clonidine, naphazoline and methoxamine as partial alpha-agonists exerting a competitive dualism in action to phenylephrine. Eur J Pharmacol. 1976 Apr;36(2):413–421. doi: 10.1016/0014-2999(76)90095-9. [DOI] [PubMed] [Google Scholar]
- Spedding M., Weetman D. F. The presence of -adrenoceptors in the guinea-pig seminal vesicle. Br J Pharmacol. 1972 May;45(1):21–28. doi: 10.1111/j.1476-5381.1972.tb09572.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Szabadi E., Bradshaw C. M. The role of physical and biological factors in determining the time course of neuronal responses. Neuropharmacology. 1974 Jun;13(6):537–545. doi: 10.1016/0028-3908(74)90143-9. [DOI] [PubMed] [Google Scholar]
- Trendelenburg U. An analysis of the alpha- and beta-effects of isoprenaline on the isolated nictitating membraen. Naunyn Schmiedebergs Arch Pharmacol. 1974;285(4):375–393. doi: 10.1007/BF00501466. [DOI] [PubMed] [Google Scholar]