Renal tubular transport of proline, hydroxyproline, and glycine. II. Hydroxy-l-proline as substrate and as inhibitor in vivo.

Renal tubular absorption of the free amino acids L-proline, hydroxy-L-proline, and glycine in man is accomplished by a transport system exhibiting preference for this group of amino acids (1, 2). The characteristics of saturability (for L-proline transport) and selective inhibition between the constituent substrates have been demonstrated for this system in man (1). Studies in vivo in the rat (3, 4) also reveal a transport system in that animal with preference for the same three amino acids. Studies in vitro with rat kidney cortex slices (4) and other tissues (5, 6) confirm this finding and also indicate that, within the system showing group preference, there may be discrete catalytic transport sites for the individual sub-strates (4, 6). The apparent order of substrate affinities for the transport system or systems is highest for L-proline and lowest for glycine (1, 4). A maximal rate for renal tubular absorption of L-proline (Tm Pro) has been shown in man (1). In the present work the behavior of free hydroxy-L-proline as substrate and its effect as an inhibitor within the system were studied. A Tm for hy-droxyproline (Tm Hypro) was demonstrated; the imino acid was also shown to be a poor inhibitor of L-proline transport but more effective against glycine. Part I reported renal tubular transport of L-proline (1)-t Markle Scholar in Medical Sciences. Methods Subjects Four healthy adult Caucasian males between 30 and 39 years of age were studied. Two subjects (2 and 3) were given two infusions; the remaining two were given one infusion. Techniques Infusions were performed in the morning with the subjects in the resting state after an overnight fast. Sufficient water was given by mouth to ensure a diu-resis exceeding 5 ml per minute. Urine was collected by spontaneous voiding while subjects were standing. The steady state infusion technique used in these experiments has been described previously (1). Hydroxy-L-proline was given in priming doses of 0.4 to 1.2 mmoles per kg (50 to 150 mg per kg) ; the sustaining dose was 3.5 /Amoles per kg per minute. Infusion of free hydroxy-L-proline is followed about 12 hours later by muscular ache, mild pyrexia, and nausea. These sensations disappear within 24 hours. This response is dose dependent, and the two subjects who were given two infusions felt greater discomfort with the larger infusion. Hydroxyprolinuria or persistence of hy-droxyprolinemia were not observed at the time of symptoms. The origin of this reaction …