Renal kinin-prostaglandin relationship: Implications for renal function

Abstract

In 1909, Abelous and Bardier described a bloodpressure-lowering substance in human urine [1], a finding that was confirmed by Frey in 1926 [2]. Kraut, Frey, and Werle believed the hypotensive principle of urine was of pancreatic origin and named it kallikrein—a word derived from the Greek term for pancreas [3]. It is now known that kallikreins occur in plasma and in several glandular tissues, for example, kidney, pancreas, intestine, and salivary and sweat glands [4]. Kallikreins are a heterogeneous group of serine proteases that act on plasma protein substrates, kininogens, to liberate peptides termed kinins [4]. From kininogen, plasma kallikreins release the nonapeptide bradykinin, whereas glandular kallikreins release the decapeptide lysylbradykinin [4]. These peptides have a broad spectrum of biological activities, ranging from stimulation of sperm motility to inhibition of postjunctional events at the renal vascular neuroeffector junction. The discovery by Terragno et al [5] and McGiff et al [61 that bradykinin stimulates release of prostaglandins is a milestone in kinin research over the past decade, and led to the proposal that the kallikrein-kinin and arachidonateprostaglandin systems are related. It now appears that interactions of kinins and prostaglandins are a feature of biological processes as diverse as those involved in inflammation and in regulation of renal function. In this paper, we analyze the evidence for a relationship between the renal kallikrein-kinin and prostaglandin (PG) systems, and discuss the significance of such relationship with regard to renal hemodynamic and excretory functions. Figure 1 depicts the proposed relationship.