Adaptations of myocardial beta-adrenergic receptor complex in hibernating marmots
Morris, S.A.; Florant, G.; Saxon, M.; Chen, G.; Bilezikian, J.P.
American Journal of Physiology 265(6 Pt 2): R1430-R1438
1993
ISSN/ISBN: 0002-9513 PMID: 8285287 Document Number: 416401
Properties of marmot (Marmota flaviventris) myocardial beta-adrenergic receptor complex (beta-AR) were evaluated during hibernation (H), in summer (S) animals, and in animals aroused from hibernation (C). The results obtained for S and C animals were identical, and only the results for C animals are shown. In H-animal myocardial membrane preparations assayed at 37 degree C, isoproterenol-dependent adenylate cyclase activity (ACA) was consistently higher, whereas the synergistic contribution of 5'-guanylylimidodiphosphate (Gpp(NH)p) in this reaction was reduced. When assayed at 10 degree C, only the ACA in H animals responded to the combination of isoproterenol and Gpp(NH)p. In contrast, at 10 degree C, ACA in response to Gpp(NH)p alone is essentially equal in H and C animals. Hibernation did not change myocardial beta-AR receptor density or affinity. In contrast, analysis of isoproterenol displacement of (125I) iodocyanopindolol revealed that the proportion of beta-AR in the high-affinity state was substantially greater in H than in C animals, and this relationship was retained even in the presence of Gpp(NH)p. In an evaluation of the role of the GTP binding proteins that couple the beta-AR to the effector adenyl cyclase, we determined that there was no change in the cholera toxin- or pertussis toxin-dependent ADP ribosylation patterns. Immunochemical detection of the individual GTP binding proteins revealed no change in the levels of G-alpha-i-1, G-alpha-i-2, or G-alpha-i-3. In contrast, we observed a hibernation-associated decrease in G-ao associated with the plasma membrane-enriched particulate fraction. Functionally, there does not appear to be a hibernation-associated change in the activity of G-s, in that the isoproterenol-dependent ACA determined by cyc- reconstitution assay was identical for H and C animals. Moreover, these changes do not relate to an obvious difference in the amount and/or type of GTP binding protein associated with the beta-AR. The results suggest that hibernation is associated with characteristic changes in hormone-sensitive ACA that permit the animal to respond to sympathetic stimulation during arousal.