Nipecotic acid ethyl ester: a cholinergic agonist that may differentiate muscarinic receptor subtypes

Conference · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6936344

Zorn, S H; Duman, R S; Enna, S J; Krogsgaard-Larsen, P; Micheletti, R; Giraldo, E; Giachetti, A

Reports indicate that nipecotic acid ethyl ester (NAEE) displays cholinomimetic properties in vivo. In the present study a series of physiological and biochemical tests were conducted to characterize this action. NAEE had a negative inotropic effect on the guinea pig atrium, and stimulated contraction of the guinea pig ileum and isolated mouse stomach strip at concentrations similar to bethanechol (BCH). The atrial and ilial effects were reversed by atropine. Unlike BCH, NAEE had no effect on basal acid secretion in the isolated mouse stomach at concentrations < 100 ..mu..M. NAEE was more potent than carbachol (CCH) in displacing /sup 3/H-ONB binding from rat brain membranes. The potency of NAEE to inhibit antagonist binding in rat heart membranes was enhanced by Mg/sup + +/ (Hill coefficient < 1.0) and reduced by Gpp(NH)p. Like CCH, NAEE inhibited GTP-stimulated adenylate cyclase in rat brain striatal membranes. As compared to CCH, NAEE had little effect (< 5%) as a stimulator of inositol phosphate (IP) production in rat brain slices. The results indicate that NAEE is a direct-acting muscarinic receptor agonist. Moreover, its differential effects on acid secretion, IP accumulation, and adenylate cyclase suggest that it may be useful for defining cholinergic receptor subclasses.

• Research Organization: Univ. of Texas Medical School, Houston
• OSTI ID: 6936344
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CHOLINE
DIGESTIVE SYSTEM
DRUGS
ESTERS
GASTROINTESTINAL TRACT
GUINEA PIGS
HEART
HYDROXY COMPOUNDS
IN VIVO
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MICE
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
QUATERNARY COMPOUNDS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
STOMACH
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES