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Cardiovascular responses to intrathecal neuropeptide γ in conscious rats: receptor characterization and mechanism of action
Author(s) -
Poulat Philippe,
Champlain Jacques,
Couture Réjean
Publication year - 1996
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.1476-5381.1996.tb15184.x
Subject(s) - medicine , endocrinology , phosphoramidon , phentolamine , hexamethonium , propranolol , neuropeptide , mechanism of action , receptor , pharmacology , chemistry , endothelin receptor , biochemistry , in vitro
1 In the conscious rat, cardiovascular responses to intrathecally (i.t.) administered neuropeptide γ (NP γ ) were studied prior to and after the i.t. pretreatment with selective antagonists at NK i ((±)‐CP 96345 and RP 67580), NK 2 (SR 48968) and NK 3 (R 486) receptors. Pretreatment with a mixture of peptidase inhibitors (phosphoramidon, captopril, bacitracin, phenanthroline) was also tested to ascertain whether or not the effect of NP γ was mediated by a metabolite. The involvement of peripheral catecholamines was examined with intravenous injection of α‐adrenoceptor (phentolamine) and β‐adrenoceptor (propranolol) antagonists. 2 NP γ (0.078‐78 nmol) induced dose‐dependent increases in heart rate (HR) and mean arterial blood pressure (MAP). The highest dose of 78 nmol did not induce an increase of MAP greater than that with 7.8 nmol but was preceded by a transient decrease of MAP (1–3 min). No desensitization was observed when three injections of 7.8 nmol NP γ were given at 90 min intervals. 3 Cardiovascular and behavioural (biting/scratching) effects evoked by 0.78 nmol NP γ were significantly reduced by the NK 1 antagonists, (±)‐CP 96345 (65 nmol) or RP 67580 (7.8 and 78 nmol). However, cardiovascular responses to NP γ were not affected by (±)‐CP 96345 (6.5 nmol), SR 48968 (7.8 and 78 nmol) or R 486 (25 nmol). Pretreatment with peptidase inhibitors significantly enhanced the cardiovascular and behavioural responses to NP γ . 4 The pressor response to 7.8 nmol NP γ was converted to a vasodepressor response by pretreatment with phentolamine (2 mg kg −1 , i.v.) while the chronotropic response was markedly reduced by propranolol (2 mg kg −1 , i.v.). 5 These results suggest that the cardiovascular responses to i.t. NP γ are mediated by NK 1 receptors in the spinal cord leading to the peripheral release of catecholamines from sympathetic fibres or the adrenal medulla. It is unlikely that the spinal action of NP γ results from its metabolic conversion into neurokinin A or another major metabolite.