anandamide and endomorphin-1

1. Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at micro-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB(1) receptor agonist) and endomorphin-1 (EM-1; a micro-opioid receptor agonist) after intrathecal administration. 2. Nociception was assessed by the paw-withdrawal test after carrageenan-induced inflammation in male Wistar rats. 3. Endomorphin-1 (16.4 pmol to 16.4 nmol) and AEA (4.3-288 nmol) alone dose-dependently decreased carrageenan-induced thermal hyperalgesia, although the highest dose of AEA also exhibited pain-inducing potential. The potency of AEA was approximately 59-fold lower than that of EM-1 (35% effective dose (ED(35)) 194.4 vs 3.3 nmol, respectively). Coadministration of these ligands revealed that combinations of 16.4 pmol EM-1 plus 28.8 or 86.5 nmol AEA were more effective than either drug alone, but other combinations were no more effective than the administration of EM-1 itself. Therefore, coadministration of AEA did not significantly shift the dose-response curve to EM-1. 4. The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB(1) receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.

Topics: Analgesics; Animals; Arachidonic Acids; Carrageenan; Drug Combinations; Drug Evaluation, Preclinical; Drug Interactions; Endocannabinoids; Hyperalgesia; Inflammation; Injections, Spinal; Male; Oligopeptides; Pain; Polyunsaturated Alkamides; Rats; Rats, Wistar; Spine; Time Factors

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