Permeable analogues of cGMP promote hepatic calcium inflow induced by the synergistic action of glucagon and vasopressin but inhibit that induced by vasopressin alone

• Published in: Biochemical journal Vol. 330 ( Pt 2); no. 2; pp. 877 - 880
• Main Authors: Nguyen, L, Karjalainen, A, Milbourne, E A, Bygrave, F L
• Format: Journal Article
• Language: English
• Published: England 01.03.1998
• Subjects: Animals; Calcium - metabolism; Cyclic GMP - analogs & derivatives; Drug Synergism; Glucagon - pharmacology; Liver - drug effects; Liver - metabolism; Male; Molsidomine - pharmacology; Nitric Oxide - metabolism; Perfusion; Rats; Rats, Wistar; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology; Vasopressins - pharmacology
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3300877

Treatment of perfused rat liver with the nitric oxide-generating reagent molsidomine led to substantial increases in cGMP without itself affecting basal Ca2+ fluxes. Under these conditions the ability of glucagon plus vasopressin to induce Ca2+ influx was greatly enhanced. The permeable analogue of cGMP (8-bromo-cGMP) enhanced glucagon plus vasopressin-induced Ca2+ influx to a similar extent as that with molsidomine. This suggests that the effect of the latter is attributable to the generation of cGMP which itself enhances the ability of the two hormones to induce synergistic Ca2+ influx. While 8-bromo-cGMP (or molsidomine) did not influence Ca2+ fluxes induced by glucagon, these agents strongly inhibited Ca2+ influx induced by vasopressin alone. These data show that while 8-bromo-cGMP has no effect on basal Ca2+ fluxes, it is able to modify the Ca2+ influx induced by glucagon and vasopressin action in hepatic tissue.