Extrasynaptic location of alpha-2 and noninnervated beta-2 adrenoceptors in the vascular system of the pithed normotensive rat
Wilffert, B.; Timmermans, P.B.; van Zwieten, P.A.
Journal of Pharmacology and Experimental Therapeutics 221(3): 762-768
1982
ISSN/ISBN: 0022-3565 PMID: 6283062 Document Number: 184476
The receptors involved in the pressor and tachycardic effects of catecholamines applied systemically or released from sympathetic nerve endings were compared. I.v. (-)-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 1-(7-methylindan-4-yloxy)-3-isopropylamino butan-2-ol 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 was confirmed by pretreatment with reserpine and removal of the adrenals. After bilateral adrenalectomy, a release of mainly norepinephrine occurred, 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 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.