Effects of mu, kappa or delta opioids administered by pellet or pump on oral Salmonella infection and gastrointestinal transit.
Our laboratory has shown previously that subcutaneously implanted, slow-release morphine pellets markedly enhanced susceptibility to oral infection with Salmonella typhimurium. Further, morphine, kappa and delta opioid receptor agonists infused via osmotic minipumps were immunosuppressive. The present study compared morphine pellets to morphine pumps and also examined the differential effects of morphine versus U50,488H (kappa agonist), deltorphin II (delta2 agonist), and (D-Pen2, D-Pen5)-enkephalin (DPDPE, delta1 agonist), administered via Alzet minipumps, on oral Salmonella infection and on gastrointestinal transit. The results show that all morphine-pelleted mice (26/26) had a marked increase in Salmonella burden in the Peyer's Patches, mesenteric lymph nodes and spleen. In comparison, only 8/20 mice receiving morphine by minipump at doses ranging from 1 to 25 mg/kg/day had any culturable Salmonella in their organs and the number of bacteria was very low. The level of Salmonella colonization correlated with blood morphine levels and gut transit measured using an intragastric charcoal meal. Morphine pellets inhibited gut transit by 38%, while mice receiving morphine by minipump at doses of 1 to 25 mg/kg/day showed only a dose-dependent 7% to 17% inhibition. Mice receiving various doses of U50,488H or DPDPE had no culturable Salmonella in the three sites. Deltorphin II given by minipump resulted in a moderate level of Salmonella in the spleen. Deltorphin II and U50,488H (0.1 to 10 mg/kg/day) did not suppress gut transit. The present studies indicate that a predominantly mu opioid receptor agonist, morphine, given by slow-release pellet, potentiated Salmonella infection and inhibited gastrointestinal transit. In contrast, morphine in pumps slightly inhibited intestinal transit, but did not sensitize to Salmonella infection. A delta1 opioid receptor agonist did not sensitize to infection, and a delta2 and a kappa opioid receptor agonist had minimal effects on either parameter.
Feng
Pu
P
Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
Rahim
Rahil T
RT
Cowan
Alan
A
Liu-Chen
Lee-Yuan
LY
Peng
Xiaohui
X
Gaughan
John
J
Meissler
Joseph J
JJ
Adler
Martin W
MW
Eisenstein
Toby K
TK
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects*; D015918:Infusion Pumps, Implantable; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010581:Peyer's Patches / Q000382:microbiology; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects; D012481:Salmonella Infections, Animal / Q000382:microbiology / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D013154:Spleen / Q000382:microbiology
D000701:Analgesics, Opioid; D004343:Drug Implants; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C060209:deltorphin II, Ala(2)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-