title: Characterization of ability of various substance P antagonists to inhibit action of bombesin.
abstract: In the present study the ability of two classes of substance P (SP) antagonists to affect SP- and bombesin (Bn)-stimulated amylase release, as well as binding of 125I-Bolton-Hunter (BH)-SP and 125I-[Tyr4]Bn, was studied to determine their mechanism of action and the relationship between inhibition of the action of SP and the action of Bn. Four SP analogues ([D-Pro2,D-Phe7,D-Trp9]SP, [D-Pro2,D-Trp7,9]SP, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP, and [D-Arg1,D-Trp7,9,Leu11]SP) and two SP-(4-11) analogues ([D-Pro4,D-Trp7,9]SP-(4-11) and [D-Pro4,D-Trp7,9,10]SP-(4-11)] did not stimulate amylase release when present alone but inhibited SP- and Bn-stimulated amylase release. For each SP analogue, inhibition was specific for peptides that stimulate release by interacting with SP or Bn receptors, whereas both SP-(4-11) analogues also inhibited cholecystokinin-stimulated amylase release. Each SP analogue's inhibition of Bn-stimulated amylase release was reversible. Each analogue inhibited binding of 125I-BH-SP with the same potency as it inhibited SP-stimulated amylase release and 125I-[Tyr4]Bn binding with the same potency as it inhibited Bn-stimulated amylase. In contrast, SP itself or SP-(4-11) itself did not inhibit Bn-stimulated amylase release or binding of 125I-[Tyr4]Bn. The relative affinities of the analogues for interacting with Bn and SP receptors differed. None of the analogues increased the dissociation of bound 125I-BH-SP or 125I-[Tyr4]Bn.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
authors: R T
authors: RT
authors: Jensen
authors: P
authors: P
authors: Heinz-Erian
authors: S
authors: S
authors: Mantey
authors: S W
authors: SW
authors: Jones
authors: J D
authors: JD
authors: Gardner
mesh_terms: D000595:Amino Acid Sequence; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology; D018004:Receptors, Bombesin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D018004:Receptors, Bombesin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; D000681:Amylases; D001839:Bombesin