The synergistic action (cross-talk) of glucagon and vasopressin induces early bile flow and plasma-membrane calcium fluxes in the perfused rat liver.
A study was made of the initial responses of perfusate Ca2+ fluxes and bile flow to Ca(2+)-mobilizing agonists, following refinements to the methods for analysing these parameters in the perfused rat liver. Net Ca2+ efflux induced by vasopressin commences at 15 s, reaches a maximal rate at 35 s and declines to zero by 55 s, when Ca2+ influx commences. Vasopressin-induced increases in bile flow commence by 20 s, attain a maximal rate by 35 s and begin to decline at 50 s, to reach basal values by 90 s. Concomitant administration of glucagon modifies each of these actions of vasopressin in the following ways: it decreases by 5 s the time of onset of net Ca2+ efflux, and the time and magnitude of such efflux, and the time of onset of bile flow is decreased to 15 s, and the flow reaches maximal rates by 30 s. When the alpha 1-adrenergic agonist phenylephrine is used in place of vasopressin, Ca2+ efflux commences at 17-18 s and is greater in magnitude; little bile flow is induced by this agonist. Glucagon modifies the action of phenylephrine in the following ways: the onset of Ca2+ efflux is brought forward by 2-3 s, it is of lower magnitude and Ca2+ influx begins by 45 s; bile flow commences by 15-20 s, and reaches a maximum at 30 s, where the rate is much greater than in the absence of glucagon; this rate gradually declines to be near basal by 80 s. The onset of agonist-induced oxygen uptake was also brought forward by the co-administration of glucagon. Comparison of agonist-induced plasma-membrane Ca2+ fluxes and bile flow (with or without glucagon administration) suggests that correlations can be made between net Ca2+ fluxes and the transient increases seen in bile flow.
Division of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra.
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Karjalainen
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Bygrave
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D005934:Glucagon / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014667:Vasopressins / Q000008:administration & dosage*
D014667:Vasopressins; D010656:Phenylephrine; D005934:Glucagon; D002118:Calcium