EFFECTS OF THE OPIOID PEPTIDES [MET5]ENKEPHALIN-ARG6-PHE7 AND [MET5]ENKEPHALIN-ARG6-GLY7-LEU8 ON CHOLINERGIC NEUROTRANSMISSION IN THE RABBIT ISOLATED ATRIA

1. The effect of the opioid peptides [Met5]enkephalin-Arg6-Phe7 (MEAP) and [Met5]enkephalin-Arg6-Gly7-Leu8 (MEAGL) were compared with those of [Leu5]enkephalin and [d-Ala2, Met5]enkephalinamide (DAME) on cholinergic neuro-transmission in the rabbit isolated atria.2. Rabbit isolated atria had a resti...
Ausführliche Beschreibung

1. The effect of the opioid peptides [Met5]enkephalin-Arg6-Phe7 (MEAP) and [Met5]enkephalin-Arg6-Gly7-Leu8 (MEAGL) were compared with those of [Leu5]enkephalin and [d-Ala2, Met5]enkephalinamide (DAME) on cholinergic neuro-transmission in the rabbit isolated atria.2. Rabbit isolated atria had a resting rate of 190 beats/min. In the presence of the β-adrenoceptor antagonist propranolol (0.3 μmol/l), atria responded to electrical field stimulation with a cholinergically mediated negative chronotropic response. The opioid peptides had no effect on the resting rate, but inhibited the negative chronotropic response to field stimulation. The IC50 values for inhibiting the cholinergic responses were 1.4 μmol/l for [Leu5]enkephalin (LE), 1.4 μmol/l for MEAP, 1.3 μmol/l for MEAGL and 0.2 μmol/l for DAME. Responses of a similar magnitude to exogenous acetylcholine were unaffected.3. Thus, MEAP, MEAGL and LE had similar potencies but DAME was about seven times more potent in inhibiting cholinergic neurotransmission in the rabbit isolated atria. The site of inhibition appears to be prejunctional. Ausführliche Beschreibung