Developmental changes in alpha 1-adrenoceptor coupling to G-protein in bovine aorta.
Differences in epinephrine binding to alpha 1-adrenoceptors, epinephrine-induced contractile potency, susceptibility to phorbol ester (PDBu) modulation, and differences in membrane fluidity were studied in bovine aorta from young (3-8 weeks) and adult or mature (6-8 years) animals. Membranes prepared from aorta of adult animals exhibited a two-fold higher receptor density while [3H]prazosin affinity was unchanged. Epinephrine displacement studies revealed both high- and low-affinity binding in membranes from the aortas of young animals whereas, preparations from adult animals exhibited only a single class of low-affinity sites. In low-temperature binding studies, membranes prepared from aortas of adult animals exhibited both high- and low-affinity agonist binding, in proportions about equal to those of young animals. The ability of PDBu to uncouple alpha 1-adrenoceptor from G-protein interaction is demonstrable in young but not in adult animals which raises the possibility of prior phosphorylation of receptors in the latter tissues. Aortas from young animals showed increased contractile potency to epinephrine and, in addition, were significantly more fluid as compared to aortas from adult animals. Alterations in the membrane environment or phosphorylation state of the alpha 1-adrenoceptor may thus provide age-dependent modulation of its function.
Jagadeesh
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G
Section of Pharmacology, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA 02115.
Tian
W N
WN
Gupta
S
S
Deth
R C
RC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure*; D001667:Binding, Competitive; D002417:Cattle; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007700:Kinetics; D008560:Membrane Fluidity / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011224:Prazosin / Q000378:metabolism; D011485:Protein Binding; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013696:Temperature; D014316:Tritium
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D019204:GTP-Binding Proteins; D011224:Prazosin; D004837:Epinephrine