The effect of in vitro aging on human lung fibroblast beta-adrenergic receptor density, coupling and response.
Age-related changes in regulation of receptor response have been observed in several tissues and include regulation of beta-adrenergic receptor (beta-receptor) responses. The role of cellular aging in age-related changes in receptor response is not clear. We have examined the effect of aging in vitro on human fibroblast beta-receptor function. MRC-5 (embryonic lung) fibroblasts were aged by replication to produce cells of early, middle and late stages corresponding to the following cumulative population doublings: 15-20, 35-45 and greater than 50, respectively. Fibroblast membrane beta-receptor responses to isoproterenol (ISO, 0.1 mM) did not differ between the three stages. Adenylate cyclase responses to prostaglandin E1 (PGE1, 1 microM), guanosine triphosphate (GTP, 0.1 mM) and 5'-guanylimidodiphosphate (Gpp(NH)p, 0.1 mM) were also similar between the stages. Beta-receptor density (Bmax) was unaffected by in vitro aging. Beta-receptor agonist affinity, an indication of the capacity for beta-receptor coupling to the nucleotide binding protein (NS), was also unaffected by cell aging. These findings suggest that cellular aging in fibroblasts alone is not accompanied by changes in beta-receptor function.
Kilfeather
S A
SA
Department of Clinical Pharmacology, Royal College of Surgeons, Dublin, Ireland.
Collins
D
D
McCormack
P
P
Cotter
T
T
O'Malley
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000527:Alprostadil / Q000494:pharmacology; D002460:Cell Line; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010869:Pindolol / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D010869:Pindolol; D000262:Adenylyl Cyclases; D000527:Alprostadil; D007545:Isoproterenol