Cerebral, spinal and peripheral inhibition of gastrointestinal transit by PI017: differential antagonism by naloxonazine

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

OSTI ID:7092739

Williams, C L; Heyman, J S; Porreca, F; Burks, T F

The authors were interested in characterizing the relative importance of central (cerebral, spinal) and peripheral opioid receptors in inhibition of gastrointestinal transit. The mu-receptor selective agonist, (NMePhe/sup 3/,D-Pro/sup 4/)morphiceptin (PL017), was evaluated for its effectiveness in slowing gastrointestinal transit after subcutaneous, intracerebroventricular (i.c.v.) or intrathecal (i.th.) administration when given alone or after pretreatment with naloxonazine, an irreversible mu/sub 1/ selective opioid receptor antagonist. Male, ICR mice (20-25 g) were pretreated with saline, naloxone or naloxonazine (35 mg/kg, s.c.) 25 hr prior to testing. Gastrointestinal transit was evaluated in previously fasted (18 hr) mice by oral administration of a liquid radiolabelled marker (Na/sub 2//sup 51/CrO/sub 4/). I.th. PL017 (100-1000 ng) was effective in slowing transit, but was essentially insensitive to naloxone or naloxonazine pretreatment. PL017 produced a dose-related inhibition of transit when given by either the i.c.v. (100-1000 ng) or s.c.(1-10 mg/kg) route; this effect was not sensitive to naloxone pretreatment but was antagonized by naloxonazine. These results indicate that the opioid receptors mediating gastrointestinal transit in the brain and periphery may be mu/sub 1/. In contrast, the insensitivity to naloxonazine suggests that the gastrointestinal effects of PL017 in the spinal cord may be the result of activation of mu/sub 2/ or possibly delta opioid receptors.

• Research Organization: Univ. of Arizona Health Sciences Center, Tucson
• OSTI ID: 7092739
• Report Number(s): CONF-8604222-; TRN: 87-008628
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
OPIUM
INTESTINAL ABSORPTION
RECEPTORS
BIOCHEMICAL REACTION KINETICS
BRAIN
CHROMIUM 51
DOSE-RESPONSE RELATIONSHIPS
GASTROINTESTINAL TRACT
INHIBITION
MICE
ORAL ADMINISTRATION
SPINAL CORD
TRACER TECHNIQUES
ABSORPTION
ANALGESICS
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHROMIUM ISOTOPES
DIGESTIVE SYSTEM
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NARCOTICS
NERVOUS SYSTEM
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
UPTAKE
VERTEBRATES
550201* - Biochemistry- Tracer Techniques