Inhibition of renal tubular transport of morphine by β-diethylaminoethyl diphenylpropylacetate in the chicken

Abstract

The Sperber preparation in the chicken was used to study the effects of β-diethylaminoethyl diphenylpropylacetate (SKF 525A) and N-methyl-3-pipendyl- N′, N′-diphenylcarbamate (MPDC) on the morphine-morphine ethereal sulfate system. Both SKF 525A and MPDC had the pharmacologic effect of opening the venous valve, which caused more blood to bypass the peritubular capillary network of the kidney. This effect was manifested by a decrease in the apparent tubular excretion fraction (ATEF) for p-aminohippuric acid. In spite of the presence of this effect, SKF 525A and MPDC produced a large fall relative to PAH in the ATEF for 14C excretion during [ 14C]-morphine infusion. The results meant that SKF 525A and MPDC blocked the access of [ 14C]morphine into the renal tubular cell. Because of the presence of this block, excretion of [ 14C]morphine and [ 14C]morphine ethereal sulfate decreased. In this situation, the decrease in metabolite formation was not due to inhibition of metabolism, but was the result of inhibition of transport of morphine into the cell. Since this block extends to tetraethyl-1-[ 14C] ammonium transport, both SKF 525A and MPDC act on the cationic transport system. The implications of this finding deserve emphasis. It was further demonstrated that [ 14C]pentobarbital was neither transported nor metabolized by the kidney. But, SKF 525A and MPDC did inhibit metabolism of [ 14C]pentobarbital, metabolism which was taking place in organs other than the kidney.