The spinal cord as a site of opioid effects on gastrointestinal transit in the mouse

Frank Porreca, T. F. Burks

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Intrathecal (i.t.) administration of morphine (1, 3, or 10 μg) effectively inhibited the passage of a radiolabeled marker through the gastrointestinal tract of mice. This effect was reversed by pretreatment with naloxone (2 mg/kg s.c.). Transection of the spinal cord at the level of the second thoracic vertebra (T2) slowed control transit when measured after 4 hr; nevertheless, i.t. morphine inhibited transit in these paralyzed animals. Similarly, i.c.v. administration of morphine (1, 3, or 10 μg) inhibited transit regardless of whether the spinal cord was transected at T2. Lower efficacy was seen with i.p. (10-300 μg/kg) or i.v. (10 μg) morphine than with comparable doses given i.t. (10 μg). Intrathecal administration (1, 3, or 10 μg) of the proposed selective delta opioid agonist peptides, D-Ala2-D-Leu5-enkephalin, D-Pen2-L-Cys5-enkephalin or i.t. administration of D-Ser2-Leu-enkephalin-(Thr6)(10 μg) were effective in inhibiting gastrointestinal transit. In contrast, the proposal kappa agonists, ketocyclazocine (1, 3 or 10 μg) or dynorphin-(1-13)(1, 10 or 100 μg), did not affect transit after i.t. administration. Dynorphin-(1-13)(10, 30 or 100 μg) or dynorphin-(1-9)(10, 30 or 100 μg) similarly did not affect transit after i.c.v. administration. Whereas D-Ala2-D-Leu5-enkephalin (1, 3, or 10 μg) and D-Ser2-Leu-enkephalin-(Thr6)(10 μg) were also efficacious in inhibiting transit by the i.c.v. route, the more delta selective D-Pen2-L-Cys5-enkephalin (1, 3, 10 or 20 μg) was not. Intracerebroventricular D-Pen2-L-Cys5-enkephalin (3, 10 or 20 μg) was effective in producing analgesia (52°C hot-plate test). These results suggest that (1) the spinal cord is a discrete and independent site of opioid effects on gastrointestinal motility; (2) opioids that are effective at one site are not always effective at the other; (3) delta opioid receptors in the brain may mediate analgesia, but not gastrointestinal effects; and (4) the effects on gut transit initiated by i.t. opioids are probably mediated by mu and delta, but not kappa, opioid receptors.

Original languageEnglish (US)
Pages (from-to)22-27
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume227
Issue number1
StatePublished - 1983

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Gastrointestinal Transit
Morphine
Opioid Analgesics
Enkephalins
Spinal Cord
Leucine Enkephalin
Analgesia
Thoracic Vertebrae
Dynorphins
kappa Opioid Receptor
delta Opioid Receptor
Gastrointestinal Motility
Opioid Peptides
Naloxone
Spinal Cord Injuries
Gastrointestinal Tract
Brain
Ala(2)-enkephalinamide-met
dynorphin (1-13)

ASJC Scopus subject areas

  • Pharmacology

Cite this

The spinal cord as a site of opioid effects on gastrointestinal transit in the mouse. / Porreca, Frank; Burks, T. F.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 227, No. 1, 1983, p. 22-27.

Research output: Contribution to journalArticle

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