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.