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Cannabinoid CB 1 receptor mediates glucocorticoid effects on hormone secretion induced by volume and osmotic changes
Author(s) -
Ruginsk SG,
Uchoa ET,
Elias LLK,
AntunesRodrigues J
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2011.05658.x
Subject(s) - endocrinology , medicine , rimonabant , glucocorticoid , dexamethasone , glucocorticoid receptor , receptor , chemistry , cannabinoid receptor , antagonist
Summary The present study provides the first in vivo evidence that the cannabinoid CB 1 receptor mediates the effects of dexamethasone on hormone release induced by changes in circulating volume and osmolality. Male adult rats were administered with the CB 1 receptor antagonist rimonabant (10 mg/Kg, p.o.), followed or not in 1 hour by dexamethasone (1 mg/Kg, i.p.). Extracellular volume expansion (EVE, 2 mL/100 g of body weight, i.v.) was performed 2 hours after dexamethasone or vehicle treatment using either isotonic (I‐EVE, 0.15 mol/L) or hypertonic (H‐EVE, 0.30 mol/L) NaCl solution. Five minutes after EVE, animals were decapitated and trunk blood was collected for all plasma measurements. Rimonabant potentiated oxytocin ( OT ) secretion induced by H ‐ EVE and completely reversed the inhibitory effects of dexamethasone in response to the same stimulus. These data suggest that glucocorticoid modulation of OT release is mediated by the CB 1 receptor. Although dexamethasone did not affect vasopressin ( AVP ) secretion induced by H ‐ EVE , the administration of rimonabant potentiated AVP release in response to the same stimulus, supporting the hypothesis that the CB 1 receptor regulates AVP secretion independently of glucocorticoid‐mediated signalling. Dexamethasone alone did not affect atrial natriuretic peptide ( ANP ) release stimulated by I‐EVE or H ‐ EVE . However, pretreatment with rimonabant potentiated ANP secretion induced by H ‐ EVE , suggesting a possible role for the CB 1 receptor in the control of peripheral factors that modulate cardiovascular function. Rimonabant also reversed the inhibitory effects of dexamethasone on H ‐ EVE ‐induced corticosterone secretion, reinforcing the hypothesis that the CB 1 receptor may be involved in the negative feedback exerted by glucocorticoids on the activity of the hypothalamic–pituitary–adrenal axis. Collectively, the results of the present study indicate that the CB 1 receptor modulates neurohypophyseal hormone secretion and systemic factors, such as corticosterone and ANP , thus participating in homeostatic responses to altered extracellular volume and plasma tonicity.