title: Adrenoceptor occupancy in isolated human fat cells and its relationship with lipolysis rate.
abstract: The relationship between lipolysis and adrenoceptor occupancy was determined in isolated human fat cells, which possess both lipolytic beta-adrenoceptors and antilipolytic alpha 2-adrenoceptors. The beta-adrenoceptor agonist, isoprenaline, and the alpha 2-adrenoceptor agonist, clonidine, had lower affinities to compete with antagonist radioligands (Ki) than to affect the rate of lipolysis (Ka). At 1 min of incubation human fat cells bound isoprenaline and clonidine with high affinity to beta- and alpha 2-adrenoceptors, respectively, but this high-affinity binding rapidly converted to a low-affinity state. The relationship between lipolysis and adrenoceptor occupancy was also assessed after long-lasting receptor inactivation. The inactivation of a small receptor fraction shifted the dose-response curves for isoprenaline and clonidine to the right but did not alter the maximum effect of the agonists (responsiveness). These results suggest that alpha 2- and beta-adrenoceptors are coupled to lipolysis according to similar models. There is a non-linear relationship between receptor and effector for both receptors, which can be explained by the co-existence of spare receptors and a transient high-affinity state of the receptors for agonists.
authors.affiliation: Department of Medicine, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Arner
authors.forename: J
authors.initials: J
authors.lastname: Hellmér
authors.forename: A
authors.initials: A
authors.lastname: Wennlund
authors.forename: J
authors.initials: J
authors.lastname: Ostman
authors.forename: P
authors.initials: P
authors.lastname: Engfeldt
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D003000:Clonidine / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D010643:Phenoxybenzamine / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010643:Phenoxybenzamine; D015016:Yohimbine; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol; D003000:Clonidine