Inhibition of pulmonary eosinophilia and airway hyperresponsiveness in allergic mice by rolipram: involvement of endogenously released corticosterone and catecholamines.
This study investigates the role of adrenal-derived catecholamines and corticosterone on the inhibition by rolipram, a phosphodiesterase (PDE)-4 inhibitor, of pulmonary eosinophilia and airway hyperresponsiveness (AHR) in allergic mice. The following experimental groups were studied in mice sensitized and challenged with ovalbumin (OVA): normal, adrenalectomized, propranolol (beta-adrenoceptor antagonist) and metyrapone (corticosterone synthesis inhibitor) treated. These interventions were studied both in the absence and in the presence of rolipram. Eosinophil numbers in the bronchoalveolar lavage (BAL) and AHR to methacholine were measured 24 h after OVA challenge. Treatment of sensitized mice with rolipram (0.3 - 10 mg kg(-1), p.o.), inhibited pulmonary eosinophilia and the AHR to methacholine in OVA-challenged mice. Adrenalectomy increased the number of eosinophils in the BAL of OVA-challenged mice but had no effect on AHR to methacholine. Adrenalectomy attenuated both the rolipram-induced inhibition of BAL eosinophilia and AHR to methacholine in OVA challenged mice. Propranolol (10 mg kg(-1), p.o.) had no effect on the inhibition of eosinophilia by rolipram but attenuated the inhibition of AHR to methacholine in OVA challenged mice. On the other hand, metyrapone (10 mg kg(-1), p.o.) attenuated the inhibition of eosinophilia by rolipram but had no effect on the inhibition of AHR to methacholine in OVA challenged mice. Metyrapone-treatment alone increased the number of eosinophils in the BAL of OVA-challenged mice. These results identify an important role for adrenal-derived catecholamines and corticosterone on the inhibition of pulmonary eosinophilia and AHR by rolipram in allergic mice.
Kung
T T
TT
Department of Allergy, Schering-Plough Research Institute Kenilworth, New Jersey, NJ 07033, USA.
Crawley
Y
Y
Luo
B
B
Young
S
S
Kreutner
W
W
Chapman
R W
RW
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D018893:Bronchoalveolar Lavage; D002395:Catecholamines / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism*; D004347:Drug Interactions; D006967:Hypersensitivity / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000517:prevention & control*; D020889:Rolipram / Q000037:antagonists & inhibitors / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D002395:Catecholamines; D010726:Phosphodiesterase Inhibitors; D011433:Propranolol; D020889:Rolipram; D003345:Corticosterone; D008797:Metyrapone