Evidence for CCKB receptors in the guinea-pig kidney: localization and characterization by [125I]gastrin binding studies and by RT-PCR

Abstract

Two types of receptors for gastrin and cholecystokinin (CCK) have been identified in the gastrointestinal tract and in the central nervous system: CCK(A) and CCK(B) receptors. Here we report evidence for the expression of CCK(B) receptors in the guinea-pig kidney. Specific binding sites for [125I]gastrin were detected in sections of the guinea-pig kidney: Binding was saturable, pH-, temperature- and time-dependent, and specific for gastrin-related peptides. The potencies for inhibition of binding of [125I]gastrin were CCK-8 > gastrin 17-I > CCK(B) receptor antagonist L-365,260 > des(SO3)CCK-8 > CCK(A) receptor antagonist L-364,718. Autoradiography demonstrated specific [125I]gastrin binding to medullary collecting ducts and to a much lesser extent to glomeruli, but not over other structures. CCK(B) receptor cDNA fragments were amplified by RT-PCR from total kidney, isolated tubuli and from tissues known to express CCK(B) receptors such as stomach and brain. The kidney might therefore be a previously unidentified site of action for gastrin and cholecystokinin-related peptides.

Expression of the cholecystokinin 2-receptor in normal human thyroid gland and medullary thyroid carcinoma

“…In recent years, it has become apparent that expression of this receptor subtype is more widespread than initially expected. Using molecular detection techniques as well as immunohistochemistry and autoradiography, expression of CCK 2 R has been detected in pancreatic acinar cells, monocytes, T lymphocytes, kidney, and in a wide variety of human tumors (7,8,19). In most of these tumors CCK 2 R expression occurs aberrantly, possibly related to dedifferentiation of the tumor cells.…”

“…In recent years, CCK 2 Rs have been detected in various extraintestinal cell types and tumors (7,8). Based on the well-established proliferative effects of gastrin, CCK 2 Rs might be important promoters of growth in these extraintestinal organs and tumors and therefore might serve as interesting diagnostic and therapeutic targets.…”

Preclinical evaluation of gastrin derivatives labelled with ¹¹¹In: Radiolabelling, affinity profile and pharmacokinetics in rats

“…This means that different mechanisms play a role in renal reabsorption of various radiolabelled peptides. Moreover, experiments in the guinea-pig kidney suggest the presence of CCK-2 receptors in the kidney, mostly over the cells of the distal collecting duct and to a much smaller degree over the glomeruli 15 . This means that at least some radioactivity in the kidney may be mediated by specific binding of the peptides to CCK-2 receptors.…”

Gastrin decreases Na+,K+-ATPase activity via a PI 3-kinase- and PKC-dependent pathway in human renal proximal tubule cells

“…The receptor of gastrin, CCKBR, has been shown to be present in the kidney to a greater extent in proximal and distal tubules and collecting ducts and to a lesser extent in glomeruli (19,27). The molecular target, the signal transduction pathway, and the mechanism of the natriuretic effect of gastrin in the kidney are not well known.…”

“…In the kidney, CCKBR is expressed to a greater extent in proximal and distal tubules and collecting ducts and to a lesser extent in glomeruli (4,27).…”