Stimulation of the hypothalamo-pituitary-adrenal axis in the rat by three selective type-4 phosphodiesterase inhibitors: in vitro and in vivo studies

British Journal of Pharmacology
M KumariJ C Buckingham

Abstract

1. Previous studies in our laboratory have shown that the synthetic xanthine analogue denbufylline, a selective type 4 phosphodiesterase (PDE-4) inhibitor, is a potent activator of the hypothalamo-pituitary-adrenal (HPA) axis when given orally or intraperitoneally (i.p.) to adult male rats. This paper describes the results of experiments in which well established in vivo and in vitro methods were used to compare the effects of denbufylline on HPA function with those of two other selective PDE-4 inhibitors, rolipram and BRL 61063 (1,3-dicyclopropylmethyl-8-amino-xanthine). For comparison, parallel measurements of the immunoreactive- (ir-) luteinising hormone (LH) were made where appropriate. 2. When injected intraperitoneally, rolipram (40 and 200 micrograms kg-1, P < 0.005), denbufylline (0.07-0.6 microgram kg-1, P < 0.05) and BRL 61063 (30 micrograms kg-1, P < 0.005) each produced marked rises in the serum ir-corticosterone concentrations. However, lower doses of rolipram (1.6 and 8 micrograms kg-1) and BRL 61063 (0.25-6 micrograms kg-1) were without effect (P > 0.05). By contrast, intracerebroventricular (i.c.v.) injection of rolipram (8 ng-1 micrograms kg-1) or denbufylline (50 ng-1 microgram kg-1) failed to influence the se...Continue Reading

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Citations

Jun 1, 2005·Pharmacology & Therapeutics·María Jesús SanzEsteban J Morcillo
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Aug 6, 2010·Journal of Applied Toxicology : JAT·Philip W Harvey, Catherine Sutcliffe
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Mar 29, 2001·Pulmonary Pharmacology & Therapeutics·J SpondM Minnicozzi
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May 24, 2011·European Journal of Endocrinology·Delphine Vezzosi, Jérôme Bertherat
Dec 20, 2007·Human Psychopharmacology·Annemarie HeberleinThomas Hillemacher
Jul 17, 2020·The Journal of Clinical Investigation·Anat Ben-ShlomoShlomo Melmed

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