Extrasynaptic location of alpha-2 and noninnervated beta-2 adrenoceptors in the vascular system of the pithed normotensive rat

Wilffert, B., Timmermans, P. B. M. W. M. & Van Zwieten, P. A., 1-Oct-1982, In : Journal of Pharmacology and Experimental Therapeutics. 221, 3, p. 762-768 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

The receptors involved in the pressor and tachycardic effects of catecholamines applied systemically or released from sympathetic nerve endings were compared. Intravenously administered (-)-epinephrine activated alpha-1, alpha-2, beta-1 and beta-2 adrenoceptors as demonstrated in pithed rats, using the alpha-1 sympatholytic drug prazosin, the alpha-2 adrenoceptor blocking substance rauwolscine, the beta-1 and beta-2 sympatholytic agent(-)-propranolol, the predominantly beta-1 adrenoceptor antagonist atenolol and the selective beta-2 adrenoceptor blocking agent ICI 118,551 as tools. (-)-Norepinephrine given i.v. proved to be an alpha-1, alpha-2 and beta-1 adrenoceptor agonist. 1,1-Dimethyl-4-phenylpiperazine iodide (DMPP) releases catecholamines from noradrenergic neurons and the adrenal medulla. The i.v. injection of DMPP into pithed rats caused an increase in diastolic pressure and heart rate by this indirect effect, which has been confirmed by pretreatment with reserpine and removal of the adrenals. After bilateral adrenalectomy, there occurred a release of mainly norepinephrine, only from the neurons. Catecholamines liberated by DMPP activated alpha-1 and beta-1 receptors and, at high doses of DMPP, alpha-2 and beta-2 adrenoceptors as well. Removal of both adrenal glands abolished the alpha-2 and beta-2 adrenoceptor-mediated effects. (-)-Norepinephrine released from neurons stimulated alpha-1 and beta-1 adrenoceptors only, although after i.v. administration of this catecholamine alpha-2 adrenoceptors were also activated. There was no indication for a beta-2 adrenoceptor-mediated vasodilation by neuronally released catecholamines. A beta-2 adrenoceptor-mediated effect, however, could be demonstrated by i.v. injection of (-)-epinephrine. The results can be explained by the presence of predominantly alpha-1 and beta-1 adrenoceptors in the postganglionic sympathetic synapses and an extrasynaptic location of alpha-2 and beta-2 adrenoceptors. The extrasynaptic receptors are possibly controlled by epinephrine from the adrenals.
Original languageEnglish
Pages (from-to)762-768
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
Publication statusPublished - 1-Oct-1982


  • 1,1 dimethyl 4 phenylpiperazinium iodide, 3 isopropylamino 1 (7 methyl 4 indanyloxy) 2 butanol, adrenalin, alpha 2 adrenergic receptor, alpha adrenergic receptor, atenolol, beta 2 adrenergic receptor, beta adrenergic receptor, heparin, hexobarbital, noradrenalin, prazosin, propranolol, rauwolscine, reserpine, tyramine, animal experiment, autonomic nervous system, blood pressure, cardiovascular system, central nervous system, heart, heart rate, intravenous drug administration, noradrenergic system, peripheral vascular system, rat, spinal animal

ID: 13988509