Differences in dihydroergotamine antagonism of glucose release by catecholamines, glucagon and adenosine 3',5'-monophosphate in rabbit liver slices.

1 Quantitative studies were made on the glucose release from rabbit liver slices in vitro induced by a range of concentrations of (-)-adrenaline (Ad), (-)-isoprenaline (Iso), glucagon and adenosine 3',5'-monophosphate (cyclic AMP) in the presence and absence of several concentrations of dihydroergotamine (DHE). 2 DHE (3.16 X 10(-6) M) shifted the Ad log concentration-response (LCR) curve to the right and also reduced the maximum response; at a higher concentration (3.16 x 10(-5) M) it produced a greater shift to the right of the LCR curve and caused a reduction in the slope and a larger depression of the maximal responses. The LCR curve to Iso was similarly affected by this higher concentration of DHE. 3 DHE (1 X 10(-5) M) produced no significant effect on the LCR curves of glucagon or cyclic AMP and even at 1 x 10(-4) M DHE caused only a slight depression of the maximal responses to both agonists without any modification of the lower major portions of the curves. 4 These data indicate a selective antagonism by DHE at the rabbit liver adrenoceptor and, since the maximal responses to catecholamines were depressed by a lower concentration of DHE than was required to produce a slight depression of the responses to glucagon and cyclic AMP, the antagonism of DHE against catecholamines does not appear to be at a site beyond the formation of cyclic AMP, but rather at a site more intimately related to the adrenoceptor.