Abstract
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 [Ile7]angiotensin III (0.01-0.3 microM) produced a non-parallel rightward displacement of the angiotensin II concentration-response curve, with a suppression of the maximum response. The potency of [Ile7]angiotensin III was increased by bacitracin and amastatin. 5. The AT1-selective non-peptide antagonist losartan (DuP 753; 0.03 and 0.1 microM) produced a parallel rightward displacement of the angiotensin II concentration-response curve, with an apparent pKB of 8.3 +/- 0.1. A higher concentration of losartan (0.3 microM) 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 AT2-selective non-peptide antagonist, PD123177 (3 microM) failed to antagonize the angiotensin II-induced depolarizations. 7. DTT (1 mM) produced a 22% reduction of the maximum response to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
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