Different mechanisms underlying reduced beta 2-adrenoceptor responsiveness in lymphocytes from neonates and old subjects.
To investigate the mechanism underlying age-dependent changes in beta-adrenoceptor function we have determined beta 2-adrenoceptor density (by (+/-)-125iodocyanopindolol (ICYP) binding) and beta 2-responsiveness (cyclic AMP responses to isoprenaline stimulation) in lymphocytes derived from 20 neonates, 54 young adults (19-30 years) and 15 old subjects (60-86 years). In young adults the mean number of lymphocyte beta 2-adrenoceptors amounted to 862 +/- 36 (range 500-1560) ICYP binding sites/cell (N = 54); it was slightly higher in old subjects with 1230 +/- 94 (698-1980) ICYP binding sites/cell (N = 15). In contrast, lymphocytes derived from neonatal blood had a significantly lower mean beta 2-adrenoceptor number (385 +/- 35 (130-608) ICYP binding sites/cell, N = 20, P less than 0.01). (-)-Isoprenaline (0.01-100 microM)-induced increases in lymphocyte cyclic AMP content were significantly lower in neonates and old subjects than in young adults. While for neonates and young adults significant positive correlations between beta 2-adrenoceptor density and 10 microM (-)-isoprenaline-induced cyclic AMP increases exist, in old subjects cyclic AMP increases were much lower than could be expected from the beta 2-adrenoceptor number. It is concluded that the mechanism underlying reduced beta 2-adrenoceptor responsiveness in neonates and old subjects is different: while in neonates it seems to be due to the reduced beta-adrenoceptor number, in old subjects it is caused by a post-receptor defect--presumably by a decreased activity of the adenylate cyclase.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008214:Lymphocytes / Q000032:analysis*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol