Binding Proteins for Dipeptides, β-Lactam Antibiotics, and p-Aminohippurate (PAH) in Plasma Membranes from Small Intestine and Kidney

Abstract

It has been suggested that orally active amino-s-lactam antibiotics and dipeptides are absorbed from the small intestine by a common H+-dependent transport system in the brush border membrane of enterocytes. Excretion of absorbed amino-s-lactam antibiotics occurs mainly in renal proximal tubules. Again, amino-s-lactam antibiotics and dipeptides share a transport system in the brush border membrane of proximal tubule cells. In the basolateral membrane the antibiotics share the transport system with p-aminohippurate (PAH). In order to identify the binding proteins possibly related to the transport of lactam antibiotics, dipeptides, and PAH, brush border and basolateral membrane vesicles were prepared and subjected to photoaffinity labelling with (3H)benzylpenicillin and the N-(4-azidobenzoyl)derivatives of cephalexin and glycyl-L-proline. With all derivatives a polypeptide of app. MW 127,000 was predominantly labelled in brush border membranes from the small intestine of rats, rabbits, and pigs. The labelling of this polypeptide was abolished by s-lactam antibiotics (penicillins and cephalosporins), dipeptides, and PAH, but not by amino acids or bile acids.