A new bioassay for glucagon

1 The relaxant action of glucagon has been studied in strips of rabbit renal arteries partially contracted by a low concentration (1 ng/ml) of noradrenaline.2 The preparation was relaxed in a dose-dependent manner by concentrations of glucagon varying between 25 ng/ml and 420 ng/ml.3 The relaxant effect of glucagon (0.1 mug/ml approximately ED(60)) on this preparation was not affected by propranolol (5.0 mug/ml), cimetidine (10 mug/ml), diphenhydramine (10 mug/ml), indomethacin (5.0 mug/ml), phentolamine (1.2 mug/ml), atropine (10 mug/ml) and 8-Leu-AT(II) (1.0 mug/ml) but was slightly potentiated by Des-Arg(9) Leu-OMe(8)-Bk (25 mug/ml) and indomethacin (50 mug/ml).4 The dose-response curve to glucagon remained parallel in the presence of papaverine (2.5 mug/ml) but was shifted to the left by a factor of 2.5 to 2.8. Theophylline (250 mug/ml) also potentiated the vascular relaxation induced by glucagon.5 Insulin (10 mug/ml) did not influence the relaxant effect of glucagon.6 The removal of the N-terminal amino acid (His) of glucagon reduced by 89% the biological activity of this fragment on the vascular preparation. The removal of the C-terminal amino acids Met-27, Asn-28 and Thr-29 of glucagon resulted in a fragment which was inactive either as an agonist or as an antagonist when tested at concentrations as high as 925 ng/ml.7 It is concluded that the relaxation of partially contracted strips of rabbit renal arteries by glucagon constitutes a simple, sensitive, relatively specific and reliable bioassay which may be useful for the determination of glucagon in biological materials and for structure-activity relationship studies with this hormone.