Stimulation of kappa opiate receptors in intestinal wall affects stress-induced increase of plasma cortisol in dogs.
In dogs, an acoustic stress (A.S.) produced by hearing of intense music (less than or equal to 90 dB) through earpieces for 1 h induced a 520% maximal rise in plasma cortisol 15-30 min after the beginning of stress. Oral administration of the specific kappa agonists, U-50488 (0.1 mg/kg) and PD 117302 (0.05 mg/kg), 30 min before the A.S. session reduced significantly (P less than 0.01) by 71.2% and 80.9% the maximal increase of plasma cortisol but did not affect the increase observed after intracerebroventricular administration of ovineCRF (100 ng/kg). These effects which are not reproduced by intravenous administration of the drugs at similar doses, were blocked by previous treatment with MR 2266 (0.1 mg/kg) or local anesthesia and vagotomy, suggesting that kappa opioid agonists inhibit the stress-induced activation of the hypothalamo-pituitary-adrenocortical (HPA) system by acting selectively on specific receptors located in the wall of the proximal gut.
Gué
M
M
Department of Pharmacology INRA, Toulouse, France.
Alvinerie
M
M
Junien
J L
JL
Buéno
L
L
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000161:Acoustic Stimulation; D000284:Administration, Oral; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004285:Dogs; D006854:Hydrocortisone / Q000097:blood*; D007276:Injections, Intraventricular; D007422:Intestines / Q000187:drug effects / Q000294:innervation*; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D013315:Stress, Psychological / Q000378:metabolism*; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology
D011758:Pyrroles; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D013876:Thiophenes; C054718:PD 117302; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone