Stimulation and inhibition of cAMP accumulation by glucagon in canine hepatocytes.

摘要: We have examined, by use of isolated canine hepatocytes and selected hormone analogs, the mechanisms which glucagon modifies accumulation cellular cAMP. Low concentrations (less than or equal to 3 nM) enhanced hepatocyte cAMP, whereas higher diminished effectiveness lower ones. This biphasic concentration dependence was observed as well for some but not others, apparent cells incubated in presence absence theophylline. Glucagon at high (greater 10 also inhibited cAMP induced isoproterenol. The inhibitory effect both these systems reversed attenuated cell incubations involving pertussis toxin (islet-activating protein) a peptide antagonist glucagon-adenylyl cyclase system. conclude that (a) glucagon, through its interaction with low affinity binding sites, can either stimulate inhibit production cAMP; (b) action appears arise from interactions ligand subset sites require structural characteristics addition those determine receptor per se; (c) adrenergic involved stimulating are linked, least regard negative glucagon.