enkephalin--ala(2)-mephe(4)-gly(5)- and anandamide

Beta-endorphin, deltorphin II, [D-Ala2, Phe4, Gly5-ol-enkephalin (DAGO) as well as endomorphin-1 and endomorphin-2 injected intracerebroventricularly (i.c.v.) induced gastroprotective action. It has been raised that endogenous opioids may have a central role in maintaining gastric mucosal integrity. Therefore we aimed to study the role of endogenous opioid system in the gastroprotective action induced by activation of alpha 2-adrenoceptors, nociceptin- and cannabinoid-receptors. Our results suggest that the non-selective opioid receptor antagonist naloxone (27 nmol i.c.v.) and the delta-opioid receptor antagonist naltrindole (5 nmol i.c.v.) abolished the mucosal protective effect of alpha 2-adrenoceptor agonists clonidine (470 pmol i.c.v.) and rilmenidine (45 pmol i.c.v.), nociceptin (1 nmol i.c.v.) and the cannabinoid receptor agonist anandamide (110 nmol i.c.v.). Based on our findings it can be raised that opioid system besides its well known regulatory functions might be involved in maintenance of gastric mucosal integrity.

Topics: Animals; Arachidonic Acids; beta-Endorphin; Clonidine; Endocannabinoids; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Ethanol; Excitatory Amino Acids; Gastric Mucosa; Injections, Intraventricular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Neurotransmitter Agents; Nociceptin; Oligopeptides; Opioid Peptides; Oxazoles; Polyunsaturated Alkamides; Rats; Rats, Wistar; Receptors, Opioid; Rilmenidine; Stomach Ulcer

In vitro receptor binding and quantitative autoradiography were used to assess the pre- and postsynaptic distribution of cannabinoid receptors in the cervical dorsal horn of the rat spinal cord. An extensive unilateral dorsal rhizotomy was performed across seven or eight successive spinal segments from C3 to T1 or T2. The densities of cannabinoid and mu opioid receptors in the central (C6) spinal segment were assessed 2, 4, 8, and 16 days post rhizotomy and compared with those of untreated rats. Rhizotomy induced approximately a 50% ipsilateral loss in the [3H]CP55,940 binding to spinal cannabinoid receptors that was maximal at 8 days post-rhizotomy. By comparison, the binding of [3H][d-Ala2-MePhe4, Gly-ol5]enkephalin (DAMGO) to mu receptors was depleted approximately 60% in near-adjacent sections. By contrast, changes in [3H]CP55,940 binding contralateral to the deafferentation were largely absent at all post-lesion delays. These data suggest that under conditions in which a spinal segment is completely deafferented, approximately 50% of cannabinoid receptors in the cervical (C6) dorsal horn reside presynaptically on central terminals of primary afferents. The present data provide anatomical evidence for presynaptic as well as postsynaptic localization of cannabinoid receptors in the spinal dorsal horn.

Topics: Analgesics; Analgesics, Opioid; Animals; Arachidonic Acids; Autoradiography; Calcium Channel Blockers; Cyclohexanols; Endocannabinoids; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Functional Laterality; Male; Neurons, Afferent; Polyunsaturated Alkamides; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Receptors, Drug; Receptors, Opioid, mu; Rhizotomy; Spinal Cord; Tritium