Pharmacological responses of α-human atrial natriuretic peptide (α-hANP) and salmon calcitonin (s-CT) were estimated following intranasal (i. n.) administration with and without poly-L-arginine (poly-L-Arg) in rats. Maximum urine flow rate after i. n. administration of α-hANP (100 μg/kg) with poly-L-Arg was 2.5 times higher than that of α-hANP alone (control) or with bestatin, an enzymatic inhibitor. Surprisingly, the total urine volume (% volume against control) for the enhancer group was comparable or more than that after i. v. injection of α-hANP (100 μg/kg). On the other hand, maximum decrease of plasma calcium level after i. n. administration of s-CT (10 ID/kg) with poly-L-Arg was greater than that of s-CT alone and the decreased calcium level continued until at least 6h. The total calcium decreasing until 41h was about 23.5% and the same to that after i. v. injection of s-CT alone (13.4IU/kg), as reported previously. These results suggest that poly-L-Arg is very useful as a nasal absorption enhancer for improving pharmacological action of peptide drugs.
