Impaired responsiveness to the effect of glucagon on plasma adenosine 3':5'-cyclic monophosphate in normal man

Small doses (10-150 microgram; 3-45 nmol) of glucagon caused a dose-dependent increase in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) concentration when injected into man. Infusion of glucagon (75 ng min-1 kg-1) for 2 h into normal subjects resulted in an initial increase in plasma cyclic AMP concentration, then a decline despite continuation of the hormone infusion and maintenance of high concentrations of circulating immunoreactive glucagon. When an injection of glucagon was given at the termination of such an infusion, the subsequent increase in plasma cyclic AMP concentration was markedly reduced when compared to that observed after a control injection which had not been preceded by a glucagon infusion. When the glucagon was injected at the end of an infusion of 1000 MRC units of bovine parathyroid hormone (BPTH) over 2 h, the plasma cyclic AMP response was normal. Conversely, after infusion of glucagon the response to injected BPTH was normal. This impairment of response was therefore specific to the hormone that had been administered and was not due to altered metabolism of circulating cyclic AMP. This phenomenon may be important in the regulation of the hormonal response by the target tissue.