A NEW BIOASSAY FOR GLUCAGON

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Abstract
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. The preparation was relaxed in a dose‐dependent manner by concentrations of glucagon varying between 25 ng/ml and 420 ng/ml. The relaxant effect of glucagon (0.1 μg/ml ≅ ED60) on this preparation was not affected by propranolol (5.0 μg/ml), cimetidine (10 μg/ml), diphenhydramine (10 μg/ml), indomethacin (5.0 μg/ml), phentolamine (1.2 μg/ml), atropine (10 μg/ml) and 8‐Leu‐ATII (1.0 ng/ml) but was slightly potentiated by Des‐Arg9 Leu‐OMe8‐Bk (25 μg/ml) and indomethacin (50 μg/ml). The dose‐response curve to glucagon remained parallel in the presence of papaverine (2.5 μg/ml) but was shifted to the left by a factor of 2.5 to 2.8. Theophylline (250 μg/ml) also potentiated the vascular relaxation induced by glucagon. Insulin (10 μg/ml) did not influence the relaxant effect of glucagon. 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. 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.