Desensitization of the beta-adrenoceptor of lymphocytes from normal subjects and asthmatic patients in vitro.
1 A lymphocyte culture method has been developed for studying in vitro the effect of prolonged exposure (24 h) to isoprenaline (10(-8) to 10(-6) mol/l) and prostaglandin E1 (PGE1; 2.8 x 10(-6) mol/l). 2 The cyclic AMP response to isoprenaline is reduced by prolonged exposure to isoprenaline. The degree of desensitization is in proportion to the concentration of isoprenaline in the culture medium. 3 Culture with isoprenaline does not reduce the cyclic AMP response to PGE1. 4 Culture for 24 h with PGE1 (2.8 x 10(-6) mol/l) reduces the cyclic AMP response to PGE1. It also significantly reduces the response to isoprenaline. 5 Lymphocytes from asthmatic patients show a similar degree of desensitization to isoprenaline (after 24 h culture with isoprenaline) to that seen in lymphocytes from normal subjects. 6 A modified assay for phosphodiesterase (PDE) activity was developed. PDE activity increased 24.5% (P less than 0.02) after culture with PGE1 but was not significantly affected by culture with isoprenaline. 7 It is concluded that desensitization caused by prolonged exposure to various stimulators of adenylate cyclase is an event dependent on several components, not all of which are yet defined.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011458:Prostaglandins E / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011458:Prostaglandins E; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D007545:Isoproterenol