Effect of beta-adrenergic receptor blockade or refractoriness induced by isoproterenol on growth of keratinocytes in vitro.
Almost complete suppression of beta-adrenergic sensitivity of adenylate cyclase was produced in keratinocytes growing on collagen gels either by induction of refractoriness by isoproterenol or by receptor blockade by propranolol, these drugs being introduced 3 days post-plating and continuously thereafter. Neither of these two manoeuvres affected growth of the keratinocytes. Despite this suppression, basal levels of cyclic AMP never fall below the levels observed in untreated cultures. On the other hand, growth inhibition is observed if isoproterenol or propranolol is added on plating. When keratinocytes are seeded on 3T3 fibroblast feeder layers, isoproterenol enhances colony growth, as reported elsewhere, indicating that the effects of isoproterenol are therefore modulated by the culture surface. In either of these in vitro model systems studied (collagen or feeder layers), no mechanism was obvious that would account for propranolol-induced psoriasiform lesions observed in vivo.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol