Premium
Pharmacological characterization of angiotensin‐induced depolarizations of rat superior cervical ganglion in vitro
Author(s) -
Hawcock A.B.,
Barnes J.C.,
Michel A.D.
Publication year - 1992
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.1476-5381.1992.tb09039.x
Subject(s) - angiotensin ii , angiotensin iii , losartan , endocrinology , chemistry , medicine , angiotensin receptor , saralasin , renin–angiotensin system , angiotensin ii receptor type 1 , pharmacology , biology , blood pressure
1 The depolarizing responses to angiotensin II and angiotensin III of the rat superior cervical ganglion have been characterized in vitro , by the use of peptidase inhibitors, peptide and non‐peptide antagonists and dithiothreitol (DTT). 2 Angiotensin II and III depolarized the ganglion in a concentration‐related manner. Angiotensin II was approximately 30 fold more potent than angiotensin III. 3 The endopeptidase inhibitor, bacitracin, increased the potency of angiotensin II and III by approximately 4 and 20 fold respectively. The aminopeptidase inhibitor, amastatin, further increased the potency of angiotensin III (but not angiotensin II) by approximately 4 fold. In the presence of bacitracin and amastatin, angiotensin II and III were equipotent. 4 The peptide antagonist [Il 7 ]angiotensin III (0.01–0.3 μ m ) produced a non‐parallel rightward displacement of the angiotensin II concentration‐response curve, with a suppression of the maximum response. The potency of [Ile 7 ]angiotensin III was increased by bacitracin and amastatin. 5 The AT 1 ‐selective non‐peptide antagonist losartan (DuP 753; 0.03 and 0.1 μ m ) produced a parallel rightward displacement of the angiotensin II concentration‐response curve, with an apparent pK B of 8.3 ± 0.1. A higher concentration of losartan (0.3 μ m ) depressed the maximum agonist response by 32 ± 6.5%, possibly reflecting non‐competitive behaviour of the antagonist. The potency of losartan was not influenced by bacitracin. 6 The AT 2 ‐selective non‐peptide antagonist, PD123177 (3 μ m ) failed to antagonize the angiotensin II‐induced depolarizations. 7 DTT (1 m m ) produced a 22% reduction of the maximum response to angiotensin II. 8 We conclude that the angiotensin II‐induced depolarizations of the rat superior cervical ganglion are mediated by angiotensin II receptors of the AT 1 subclass. The ability of peptidase inhibitors to modify the potency of peptide agonists and antagonists highlights the difficulties associated with the use of peptide agents to characterize angiotensin II receptors in this preparation.