Forskolin potentiates isoproterenol induced beta adrenoceptor desensitization in intact human lymphocytes.
The effects of forskolin on L-isoproterenol induced beta adrenoceptor desensitization in intact human lymphocytes from healthy subjects were studied. Exposure of intact lymphocytes to 50 microM L-isoproterenol for 150 minutes at 37 degrees C induced a 18% loss in beta adrenergic receptor density (Bmax) as characterized by using [3H]-DHA at 25 degrees C (23% loss, at 4 degrees C) as well as a significant loss in cyclic AMP responsiveness of the cell to isoproterenol restimulation. The addition of 10 microM forskolin to 50 microM isoproterenol potentiated isoproterenol induced beta 2 adrenoceptor desensitization as shown by further reduction in [3H]-DHA binding sites (decreased by 40% at 25 degrees C, 45% at 4 degrees C) and corresponding decrease in cyclic AMP responsiveness. These suggest that isoproterenol and forskolin act in a cooperative manner not only in the activation of adenylate cyclase and cyclic AMP generation but also in the regulation of hormone receptor and adenylate cyclase coupling.
Yu
J L
JL
Department of Medicine, UCLA School of Medicine 90024.
Hui
K K
KK
D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP; D007545:Isoproterenol