The expression of alpha 1 adrenoceptor subtypes changes with age in the rat aorta.
Previous studies showed that alpha 1 adrenoceptor-mediated contractile responses change with age in the rat aorta, becoming more sensitive to Ca++ channel blockers and less sensitive to chlorethylclonidine (CEC), suggesting a change in the alpha 1 adrenoceptor subtypes that are present. In this study, alpha 1 adrenoceptor density and alpha 1 adrenoceptor subtypes were measured in the Fischer 344 rat aorta during aging. Aortic alpha 1 adrenoceptor densities, determined by saturation binding of 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl] tetralone ([125I]-HEAT), were 47, 41 and 45 fmol/mg protein in 1-,6- and 24-month-old rats, respectively. The noncompetitive antagonist CEC completely blocked [125I]-HEAT binding in aortas from 1-month-old rats but inhibited binding only partially in aortas from older rats. Two binding sites were detected for norepinephrine and for WB4101 in all ages. The low-affinity constants for WB4101 (31-51 nM) were consistent with those for the alpha 1b adrenoceptor subtype, and this binding site decreased with age. The high-affinity constant for WB4101 (1.4 nM) in 1-month-old aorta was consistent with that for alpha 1d adrenoceptor subtype, whereas the high-affinity constants (0.03 nM) in 6- and 24-month-old aortas were consistent with those for the alpha 1a adrenoceptor subtype. At least three alpha 1 adrenoceptor subtypes appear to be colocalized in the rat aorta, so the binding affinities may reflect binding to more than one subtype. This makes it difficult to identify denfinitively the subtypes based on their radioligand binding characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia, USA.
H
H
Gurdal
N
N
Tilakaratne
R D
RD
Brown
M
M
Fonseca
E
E
Friedman
M D
MD
Johnson
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1