Non-selective enkephalin analogs, such as [D-Ala2, Met5]enkephalinamide, have been found to increase jejunal absorption in the rat and dog after their intracerebroventricular administration. In the present investigation, experiments were designed to characterize the brain opiate receptor subtype mediating this action in the rat proximal jejunum in situ and to assess the involvement of extrinsic sympathetic nerves innervating this gut region in opioid-induced absorption. Changes in jejunal water transport were examined in rats pretreated with bolus i.c.v. doses (≤ I μg) of the respective μ-, δ-, or κ-opiate agonists [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAGO), [D-Pen2, D-Pen5]enkephalin or U-50 488 and infused intravenously with the secretagogue prostaglandin E1 (PGE1, 5 μg/kg-min). In saline-pretreated rats, PGE1 produced large, time-dependent decreases in jejunal fluid absorption. Of the opiate agonists examined, only DAGO in submicrogram doses significantly inhibited PGE1 actions 60 to 90 min after its administration. Extirpation of the celiac and superior mesenteric ganglia, major sources of sympathetic neurons innervating the upper gut, significantly attenuated both the antiabsorptive actions of PGE1 and the proabsorptive actions of DAGO (0.3 μg, i.cv.). These results suggest that CNS μ-opiate receptors modulate jejunal absorption in the rat, an action mediated through extrinsic sympathetic nerves innervating the upper small intestine.
Bibliographical noteFunding Information:
This work was funded by U.S.P.H.S. grant DK-35260 to D.R.B. anda MinnesotaVeterinaryM edicalC ouncilG raduate StudentA ward to F.L.Q. The authorst hankD r. SandraR oerig (Departmento f Pharmacology,U niversityof Minnesoda)f or her invaluableh elp with the HPLC assay.