Differential effect of stimulation strength in mouse vas deferens on inhibition of neuroeffector transmission by receptor type selective opioids

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Abstract
In the mouse isolated vas deferens the amplitude of excitatory junction potentials (e.j.p.s) recorded intracellularly from smooth muscle cells varied with the strength of stimulation. Receptor type selective opioids were tested in this preparation. The μ-agonist normorphine (2,000 nmol/l) reduced the amplitude of e.j.p.s and shifted the stimulus-response curve in a parallel way to the right. By contrast, the ϰ-agonist U-50488 (1,000 nmol/l) and the δ-agonist [d-Ala2,d-Leu5]-enkephalin (2 nmol/l) caused a nonparallel shift of the curve. In addition, opioids having a lower selectivity for one type of receptor were also used. The preferential ϰ-agonists ethylketocyclazocine (40 nmol/l) and dynorphin A1–13 (100 nmol/l) produced parallel and nonparallel shifts, respectively. Thus, normorphine and ethylketocyclazocine were more effective in depressing e.j.p.s evoked by low intensities of stimulation than those evoked by high intensities of stimulation. U-50488, dynorphin A1–13 and [d-Ala2,d-Leu5]-enkephalin caused an equal depression of e.j.p.s evoked by either intensity of stimulation. The preferential μ- and δ-antagonists naloxone (1,000 nmol/l) and ICI 154129 (10,000 nmol/l), reversed the action of the respective agonists normorphine and [d-Ala2,d-Leu5]-enkephalin. In addition, ICI 154129 (10,000 nmol/l) reversed the action of dynorphin A1–13, as well. The preferential ϰ-antagonist MR-2266 (1,000 nmol/l) prevented the effect of both ethylketocyclazocine and U-50488. It is concluded that under the conditions of these experiments normorphine and ethylketocyclazocine acted at μ-, U-50488 at ϰ-, and dynorphin A1–13 and [d-Ala2,d-Leu5]-enkephalin at δ-receptors. In the mouse vas deferens more excitable fibres are probably equally sensitive to all three types of opioids, whereas less excitable fibres seem to be more sensitive to δ- and ϰ-, than to μ-agonists.