Switching from alpha 1- to beta-subtypes in adrenergic response during primary culture of adult-rat hepatocytes as affected by the cell-to-cell interaction through plasma membranes.
The alpha 1-adrenergic response was predominant over the beta-adrenergic one in adult rat hepatocytes, when the responses were measured as the agonist-induced generations of Ins(1,4,5)P3 and cyclic AMP, respectively. During primary culture of the adult rat hepatocytes, the beta-adrenergic response developed rapidly, whereas the alpha 1-response decreased gradually. Such receptor-subtype switching did not occur unless the cells were cultured under conditions favourable for cell growth, i.e. at low cell density (10(4) cells/cm2). The switching was prevented progressively as the cell culture density was increased up to 20-fold or the low-density culture was achieved by addition of increasing amounts of liver plasma membranes. The gradual decrease in alpha 1-response was accounted for by a concurrent decrease in the receptor site density, whereas rapid development of the beta-response definitely preceded the increase in beta-ligand binding sites during the culture. This rapid development of the beta-response reflected enhanced coupling of the receptor to G-protein during the early stage of culture, as evidenced by the progressively developed ability of GTP to lower the affinity of beta-agonist binding to membranes prepared from these short-time-cultured hepatocytes.
Kajiyama
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Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Ui
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014667:Vasopressins / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D014667:Vasopressins; D000804:Angiotensin II; D010656:Phenylephrine; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; C033394:CGP 12177; D011224:Prazosin