Summary
Age-related changes in presynaptic alpha-2 and postsynaptic alpha-1 adrenoceptors have been determined using the rat isolated vas deferens and the thoracic aorta, respectively. The IC50 values of clonidine, B-HT 933 and UK 14,304 for inhibition of the electrically evoked contractions of the vas deferens were significantly higher in 50 week old rats when compared with rats of 5 weeks. Similarly, EC50 values for the contraction of the thoracic aorta by noradenaline, methoxamine and phenylephrine were significantly increased in 50 week old rats compared with 5 week old rats. No age-related changes in the potency of the selective alpha-2 adrenoceptor antagonists yohimbine and Wy 26392 were detected in the vas deferens. Similarly, there were no age-related changes in the alpha-1 adrenoceptor antagonist potency of indoramin or prazosin on the aorta.
The results of the present study suggest that the potency of both alpha-1 and alpha-2 adrenoceptor agonists, as measured by their respective EC and IC50 values decreases with increasing age.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol Chemother 14:48–58
Bertel O, Buhler FR, Kiowski W, Lutold BE (1980) Decreased beta-adrenoceptor responsiveness as related to age, blood pressure and plasma catecholamines in patients with essential hypertension. Hypertension 2(2):130–138
Brodde O-E, Analauf M, Graben N, Bock KD (1982) Age-dependent decrease of alpha-2 adrenergic receptor numbers in human platelets. Eur J Pharmacol 81:345–347
Brown J, Doxey JC, Handley S (1980) Effects of alpha-adrenoceptor agonists and antagonists and of antidepressant drugs on pre-and postsynaptic alpha-adrenoceptors. Eur J Pharmacol 67:33–40
Cambridge D,(1981) UK 14,304 a potent and selective alpha-2 adrenoceptor agonist for the characterisiation of alpha-adrenoceptor subtypes. Eur J Pharmacol 72:413–415
Cambridge D, Davey MJ, Massingham R (1977) The pharmacology of antihypertensive drugs with specific reference to vasodilators, alpha-adrenergic blocking agents and prazosin. Med J Aust (suppl) 2:2–6
Cohen ML, Berkowitz B (1974) Age related changes in vascular responsiveness to cyclic nucleotides and contractile agonists. J Pharmacol Exp Ther 191:147–155
Decker N, Ehrhardt JD, Leclerc G, Schwartz J (1984) Postjunctional alpha-adrenoceptors: alpha-1 and alpha-2 subtypes in the rat vasculature in vitro and in vivo. Naunyn-Schmiedeberg's Arch Pharmacol 326:1–6
Docherty JR, O'Malley K (1983) An examination of age-related changes in pre- and postsynaptic alpha-adrenoceptors in the rat isolated vas deferens. Eur J Pharmacol 95:171–176
Docherty JR, Hyland L (1984) Age-related changes in pre- and postsynaptic alpha-adrenoceptors in the human saphenous vein. Br J Pharmacol 84:144P
Drew MG (1976) Effect of alpha-adrenoceptor agonists and antagonists on pre- and postsynaptically located alpha-adrenoceptors. Eur J Pharmacol 36:313–320
Drew MG (1977) Pharmacological characterisation of the presynaptic alpha-adrenoceptors in the rat vas deferens. Eur J Pharmacol 42:123–130
Duckles SP, Garter BJ, Williams CL (1985) Vascular adrenergic neuroeffector function does not decline in aged rats. Circ Res 56(1):109–116
Fleisch JH (1980) Age-related changes in the sensitivity of blood vessels to drugs. Pharmacol Ther 8:477–487
Fleisch JH, Hooker CS (1976) The relationship between age and relaxation of vascular smooth muscle in the rabbit and rat. Circ Res 38:243–249
Fleisch JH, Maling HM, Brodie BB (1970) Beta-receptor activity in aorta: variations with age and species. Circ Res 26:151–162
Furchgott RF (1967) The pharmacological differentiation of adrenergic receptors. Ann NY Acad Sci 139:533–570
Gerstenblith G, Spurgeon JP, Froehlick JP, Weisfeldt ML, Lakatta EG (1979) Diminished ionotropic responsiveness to ouabain in aged rat myocardium. Cire Res 44:517–523
Guanieri T, Filburn CR, Zitnik G, Roth GS, Lakatta EG (1980) Contractile and biochemical correlates of beta-adrenergic stimulation of the aged heart. Am J Physiol 239:H501-H508
Hayashi S, Toda N (1978) Age-related changes in the response of rabbit isolated aorta to vasoactive agents. Br J Pharmacol 64:229–237
Holl JE, Mokler CM (1982) Loss of H2-histamine receptor activity in rabbit aorta after maturity. J Cardiovasc Pharmacol 4:136–141
Kobinger W, Pichler R (1977) Pharmacological characterisation of B-HT 933 as a hypotensive agent of the clonidine-type. Naunyn-Schmiedeberg's Arch Pharmacol 300:39–46
Kenakin TP (1984) The classification of drugs and drug receptors in isolated tissues. Pharmacol Rev 36(3):165–222
Lakatta EG (1980) Age-related alteration in the cardiovascular responses to adrenergic-mediated stress. Fed Proc 39:3173–3177
Lattimer N, McAdams RP, Rhodes KF, Sharma S, Turner SJ, Waterfall JF (1984) Alpha-2 adrenoceptor antagonism and other pharmacological antagonist properties of some substituted benzoquinolizines and yohimbine in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 327:312–318
McAdams RP, Lattimer N, Rhodes KF, Waterfall JF (1985) The effect of age on activation of pre- and postsynaptic alpha-adrenoceptors in the rat. Br J Pharmacol 86:494P
Palmer GJ, Zeigler MG, Lake CR (1978) Responsiveness of noradrenaline and blood pressure to stress increases with age. J Gerontol 33:482–487
Partilla JS, Hoopes MT, Ito H, Dax EM, Roth GS (1982) Loss of rat ventricular alpha-1 adrenergic receptors during aging. Life Sci 31:2507–2512
Rhodes KF, Waterfall JF (1978) Pre- and postsynaptic alpha-adrenoceptor antagonism by indoramin in isolated tissues of the rat. J Pharm Pharmacol 30:516–517
Rowe JW, Troden BR (1980) Sympathetic nervous system and ageing in man. Endoc Rev 1:167–179
Scott PJ, Reid JL (1982) The effect of age on responses of human isolated arteries to noradrenaline. Br J Clin Pharmacol 13(2):237–239
Starke K, Langer SZ (1979) A note on the terminology for presynaptic receptors. In: Langer SZ, Starke K, Dubocovich ML (eds) Advances in biosciences, vol 18. Pergamon Press, Oxford, pp 1–3
Starke K, Mantel H, Gayke W, Merker R (1974) Comparison of the effect of clonidine on pre- and postsynaptic adrenoceptors in the rabbit pulmonary artery. Naunyn-Schmiedeberg's Arch Pharmacol 285:133–150
Starke K, Borowski E, Endo T (1975) Preferential blockade of presynaptic alpha-adrenoceptors by yohimbine. Eur J Pharmacol 34:385–388
Starke K (1981) Alpha-adrenoceptor sub-classification. Rev Physiol Biochem Pharmacol 88:199–236
Stephenson RP (1956) A modification of receptor theory. Br J Pharmacol 11:379–393
Tuttle RS (1966) Age related changes in sensitivity of rat aortic strips to noradrenaline and associated chemical and structural alterations. J Gerontol 21:510–516
Williams PB (1984) Effect of age upon the uptake and binding of calcium in rat aorta. Biochem Pharmacol 33(19):3097–3099.
Zeigler MG, Lake CR, Kopin IJ (1976) Plasma noradrenaline increases with age. Nature 261:333–335
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McAdams, R.P., Waterfall, J.F. The effect of age on the sensitivity of pre- and postsynaptic alpha-adrenoceptors to agonists and antagonists in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 334, 430–435 (1986). https://doi.org/10.1007/BF00569382
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00569382