Evidence for CCK(B) receptors in the guinea-pig kidney: localization and characterization by [125I]gastrin binding studies and by RT-PCR.
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.
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
T
T
von Schrenck
A
A
de Weerth
S
S
Bechtel
T
T
Eschenhagen
J
J
Weil
G
G
Wolf
M
M
Schulz
H
H
Greten
D000450:Aldosterone / Q000494:pharmacology; D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001570:Benzodiazepinones / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D015139:Blotting, Southern; D046508:Culture Techniques; D020109:Devazepide / Q000494:pharmacology; D004347:Drug Interactions; D005755:Gastrins / Q000378:metabolism*; D006168:Guinea Pigs; D006727:Hormone Antagonists / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010671:Phenylurea Compounds / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000809:Angiotensins; D001570:Benzodiazepinones; D005755:Gastrins; D006727:Hormone Antagonists; D007457:Iodine Radioisotopes; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D000450:Aldosterone; D020109:Devazepide