Effect of methylprednisolone on recovery of beta-adrenergic desensitization in rat hearts.
The effects of methylprednisolone (Solu-Medrol, CAS 83-43-2) on isoprenaline (isoproterenol)-induced decreases in the number of beta-receptors and adenylate cyclase activities in rat hearts. Rats were divided into 4 groups: 1. the control group, untreated; 2. the ISPOd group; 3. the ISP7d group, 10 mg/kg of isoprenaline was subsequently injected once a day for 6 successive days, and rats were cervically dislocated 15 h or 7 days after the last isoprenaline injection, respectively; 4. the ISP + MP7d group, 20 mg/kg of methylprednisolone was intraperitoneally injected once a day for 7 successive days following 6 successive days of isoprenaline injection, and rats were cervically dislocated. A significant decrease in the number of beta-receptors was observed (28.9 +/- 4.2 fmol/mg protein) after 6 successive isoprenaline injections compared with the control (41.7 +/- 3.6), and this significant decrease persisted for 7 days (32.6 +/- 5.8). Administration of methylprednisolone accelerated the recovery of beta-receptors (38.4 +/- 5.1) 7 days after the last isoprenaline injection. Adenylate cyclase activities were also decreased by successive isoprenaline treatments (isoprenaline-stimulated adenylate cyclase activity, 13.9 +/- 2.7 pmol/min/mg protein; basal adenylate cyclase activity, 11.2 +/- 1.7) compared with the control (isoprenaline-stimulated, 25.7 +/- 3.7; basal, 18.1 +/- 2.4). Significant decreases in adenylate cyclase activities were observed 7 days after isoprenaline administration (isoprenaline-stimulated, 17.7 +/- 3.9; basal, 14.8 +/- 2.4). Methylprednisolone also accelerated the recoveries (isoprenaline-stimulated, 20.3 +/- 2.9; basal, 17.1 +/- 3.9). These results indicate that methylprednisolone accelerated the recovery of the decrease in beta-adrenergic responsiveness caused by successive administrations of isoprenaline.
Sugiyama
S
S
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Hayashi
K
K
Hanaki
Y
Y
Taki
K
K
Ozawa
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004082:Dihydroalprenolol / Q000493:pharmacokinetics; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000201:enzymology / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D000262:Adenylyl Cyclases; D008775:Methylprednisolone