3,5,3'-L-triiodothyronine regulation of beta-adrenergic receptor density and adenylyl cyclase activity in synaptosomal membranes of aged rats.
To determine the effect of aging on T3 up-regulation of beta-adrenergic receptor activity of purified synaptosomal membranes (SPM), beta-adrenergic receptor density (Bmax) and adenylyl cyclase (AC) activity were measured in young (6 months old) and aged (26 months old) male F-344 rats at baseline and after treatment with triiodothyronine (T3), 15 micrograms/100 g, intraperitoneally for 10 days. The Bmax (fmol/mg protein) as measured by 125I-iodocyanopindolol binding was reduced in aged rats (70.8 +/- 4.1) compared to young rats (93.5 +/- 11.2). T3 treatment resulted in a significant increase in Bmax of young rats but not in aged rats (P < 0.05). The AC activity (pmol cAMP/mg) in response to prostaglandin E1 (PGE1) was reduced in aged rats compared to young rats (67.8 +/- 2.9 vs 108.3 +/- 18.6; P < 0.01). The sodium fluoride (NaF) stimulated AC activity was not altered with age. A net isoproterenol stimulated AC activity could not be demonstrated in any age group. T3 treatment did not alter AC activity of SPM. It is concluded that aging is associated with reduced responsiveness to T3-stimulated up-regulation of beta-adrenergic receptor number in synaptosomal membranes.
Mooradian
A D
AD
St. Louis V.A. Medical Center, MO.
Scarpace
P J
PJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D020120:Iodocyanopindolol; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D020120:Iodocyanopindolol; D012969:Sodium Fluoride; D010869:Pindolol; D000262:Adenylyl Cyclases; D000527:Alprostadil