Abstract
The hypothesis that beta-adrenoceptor agonism might explain a reported lack of competitive antagonism between alpha 2-adrenoceptor antagonists and agonists of the phenylethylamine class was tested in the electrically field stimulated ileum of the guinea-pig. The beta-adrenoceptor agonist, isoprenaline, was used as the phenylethylamine and inhibition of 'twitch' response evoked by cholinergic stimulation was measured. In the presence of idazoxan (3 microM), to block inhibitory alpha 2-adrenoceptors, propranolol (0.1 to 5.0 microM) failed to act competitively toward isoprenaline. Isoprenaline responses totally resistant to inhibition by propranolol were obtained. As inhibitory alpha 1-adrenoceptors are absent from guinea-pig ileum, a recognition site distinct from the currently defined alpha- and beta-adrenoceptors is postulated. Agonism by phenylethylamine based agonists at this site may explain their inability to act competitively with alpha- and beta-adrenoceptor antagonists.
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- ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arch J. R., Ainsworth A. T., Cawthorne M. A., Piercy V., Sennitt M. V., Thody V. E., Wilson C., Wilson S. Atypical beta-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature. 1984 May 10;309(5964):163–165. doi: 10.1038/309163a0. [DOI] [PubMed] [Google Scholar]
- Bentley G. A., Starr J. The antinociceptive action of some beta-adrenoceptor agonists in mice. Br J Pharmacol. 1986 Jul;88(3):515–521. doi: 10.1111/j.1476-5381.1986.tb10231.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bojanic D., Jansen J. D., Nahorski S. R., Zaagsma J. Atypical characteristics of the beta-adrenoceptor mediating cyclic AMP generation and lipolysis in the rat adipocyte. Br J Pharmacol. 1985 Jan;84(1):131–137. [PMC free article] [PubMed] [Google Scholar]
- Bond R. A., Charlton K. G., Clarke D. E. Evidence for a receptor mediated action of norepinephrine distinct from alpha- and beta-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1986 Nov;334(3):261–266. doi: 10.1007/BF00508780. [DOI] [PubMed] [Google Scholar]
- Bond R. A., Charlton K. G., Clarke D. E. Responses to norepinephrine resistant to inhibition by alpha and beta adrenoceptor antagonists. J Pharmacol Exp Ther. 1986 Feb;236(2):408–415. [PubMed] [Google Scholar]
- Bristow M., Sherrod T. R., Green R. D. Analysis of beta receptor drug interactions in isolated rabbit atrium, aorta, stomach and trachea. J Pharmacol Exp Ther. 1970 Jan;171(1):52–61. [PubMed] [Google Scholar]
- Drew G. M., Hilditch A. Prejunctional dopamine receptors modulate twitch responses to parasympathetic nerve stimulation in the rabbit isolated rectococcygeus muscle. Br J Pharmacol. 1984 Dec;83(4):871–881. doi: 10.1111/j.1476-5381.1984.tb16526.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drew G. M. Pharmacological characterization of the presynaptic alpha-adrenoceptors regulating cholinergic activity in the guinea-pig ileum. Br J Pharmacol. 1978 Oct;64(2):293–300. doi: 10.1111/j.1476-5381.1978.tb17303.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Görich R., Weihrauch T. R., Kilbinger H. The inhibition by dopamine of cholinergic transmission in the isolated guinea-pig ileum. Mediation through alpha-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1982 Mar;318(4):308–312. doi: 10.1007/BF00501170. [DOI] [PubMed] [Google Scholar]
- Hicks P. E., Langer S. Z., Macrae A. D. Differential blocking actions of idazoxan against the inhibitory effects of 6-fluoronoradrenaline and clonidine in the rat vas deferens. Br J Pharmacol. 1985 Sep;86(1):141–150. doi: 10.1111/j.1476-5381.1985.tb09444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee R. J., Evans D. B., Baky S. H., Laffan R. J. Pharmacology of nadolol (SQ 11725), a beta-adrenergic antagonist lacking direct myocardial depression. Eur J Pharmacol. 1975 Sep-Oct;33(2):371–382. doi: 10.1016/0014-2999(75)90182-x. [DOI] [PubMed] [Google Scholar]
- Melchiorre C., Yong M. S., Benfey B. G., Belleau B. Molecular properties of the adrenergic alpha receptor. 2. Optimum covalent inhibition by two different prototypes of polyamine disulfides. J Med Chem. 1978 Nov;21(11):1126–1132. doi: 10.1021/jm00209a007. [DOI] [PubMed] [Google Scholar]
- Morris J. L., Gibbins I. L., Clevers J. Resistance of adrenergic neurotransmission in the toad heart to adrenoceptor blockade. Naunyn Schmiedebergs Arch Pharmacol. 1981;317(4):331–338. doi: 10.1007/BF00501315. [DOI] [PubMed] [Google Scholar]
- Mottram D. R. Pre-junctional alpha 2-adrenoceptor activity of B-HT920. J Pharm Pharmacol. 1983 Oct;35(10):652–655. doi: 10.1111/j.2042-7158.1983.tb02859.x. [DOI] [PubMed] [Google Scholar]
- Ruffolo R. R., Jr Interactions of agonists with peripheral alpha-adrenergic receptors. Fed Proc. 1984 Nov;43(14):2910–2916. [PubMed] [Google Scholar]
- Vizi E. S., Ludvig N., Rónai A. Z., Folly G. Dissociation of presynaptic alpha 2-adrenoceptors following prazosin administration: presynaptic effect of prazosin. Eur J Pharmacol. 1983 Nov 25;95(3-4):287–290. doi: 10.1016/0014-2999(83)90648-9. [DOI] [PubMed] [Google Scholar]
- Wikberg J. E. Pharmacological classification of adrenergic alpha receptors in the guinea pig. Nature. 1978 May 11;273(5658):164–166. doi: 10.1038/273164a0. [DOI] [PubMed] [Google Scholar]
- Wilson C., Wilson S., Piercy V., Sennitt M. V., Arch J. R. The rat lipolytic beta-adrenoceptor: studies using novel beta-adrenoceptor agonists. Eur J Pharmacol. 1984 May 4;100(3-4):309–319. doi: 10.1016/0014-2999(84)90007-4. [DOI] [PubMed] [Google Scholar]
