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Facilitation of noradrenaline release from sympathetic nerves through activation of ACTH receptors, β‐adrenoceptors and angiotensin II receptors
Author(s) -
Costa Mary,
Majewski Henryk
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11730.x
Subject(s) - endocrinology , medicine , propranolol , isoprenaline , phentolamine , chemistry , stimulation , angiotensin ii , receptor , adrenocorticotropic hormone , corticosterone , pulmonary artery , renin–angiotensin system , hormone , blood pressure
1 In rabbit pulmonary artery and left atrial strips previously incubated with [ 3 H]‐noradrenaline, the active fragment of adrenocorticotropic hormone (ACTH 1–24 , 0.1 μ m ) significantly enhanced the stimulation‐induced (S‐I) outflow of radioactivity when a cocktail containing corticosterone (40 μ m ) , cocaine (30 μ m ) and propranolol (4 μ m ) was present, but not in the absence of these drugs. In rabbit pulmonary artery a facilitatory effect of ACTH 1–24 (0.1μ m ) was also observed when only cocaine (30 μ m ) was present. 2 ACTH 1–24 (0.1 μ m ) did not affect the S‐I outflow of radioactivity from rat atria, rat pulmonary artery or guinea‐pig pulmonary artery, either in the presence or in the absence of the cocktail containing corticosterone (40 μ m ), cocaine (30 μ m ) and propranolol (4 μ m ). These results suggest that the presence of facilitatory prejunctional ACTH receptors may be restricted to rabbit sympathetic nerve endings. 3 Angiotensin II (0.01 μ m ), but not isoprenaline (0.1 μ m ) or ACTH 1–24 (0.1μ m ), significantly enhanced the S‐I outflow of radioactivity from rabbit pulmonary artery. In the presence of phentolamine (1 μ m ) to block inhibitory α 2 ‐adrenoceptors, the facilitatory effect of angiotensin II (0.01 μ m ) was significantly enhanced, and a significant facilitatory effect of isoprenaline (0.1 μ m ) and of ACTH 1–24 (0.1 μ m ) was then revealed. These results suggest that feedback inhibition of noradrenaline release, mediated through the prejunctional α 2 ‐adrenoceptor mechanism, buffers increases in noradrenaline release during activation of facilitatory prejunctional receptors. 4 In rabbit pulmonary artery, two concentrations of 8‐Br‐cyclic AMP, (270 or 540 μ m ), enhanced the S‐I outflow of radioactivity in the presence of phentolamine (1 μ m ) to a similar extent. In the presence of 8‐Br‐cyclic AMP (270 μ m ) and phentolamine, the facilitatory effects of isoprenaline (0.1 μ m ) and of ACTH 1–24 (0.1 μ m ) were blocked, whereas that of angiotensin II (0.01 μ m ) was not changed. These results suggest that both prejunctional β‐adrenoceptors and ACTH receptors enhance noradrenaline release by generating cyclic AMP. The mechanism by which angiotensin II facilitates noradrenaline release is probably independent of the cyclic AMP second messenger pathway.