Mechanism of alpha 2-adrenergic inhibition of neuroeffector transmission in the mouse vas deferens.
The process by which the activation of presynaptic alpha 2-adrenoceptors inhibits the release of noradrenaline from terminals of postganglionic sympathetic nerves was studied in the mouse isolated vas deferens. Clonidine was used as a prototypic agonist. Field stimulation-evoked excitatory junction potentials (e.j.p.s) were recorded from individual muscle cells. The e.j.p. amplitudes were taken as a measure of transmitter release. Changes in the external Ca2+ concentration from 2.5 to 1.25 or 5 mM caused corresponding changes in the size of e.j.p.s. When the normal Ca2+ concentration of the medium (2.5 mM) was substituted by equimolar quantities of Ba2+ or Sr2+, the e.j.p. amplitudes decreased considerably. Clonidine (0.3-30 nM) inhibited the nerve stimulation-evoked e.j.p. amplitudes in a concentration-dependent manner, without altering appreciably the frequency of spontaneous e.j.p.s. Procedures known to enhance Ca2+ entry into nerve terminals, like a high Ca2+ medium (Ca2+ 5 mM) or 4-aminopyridine 30 microM reduced the effect of clonidine. Repetitive nerve stimulation at 3 Hz, which is supposed to lead to an accumulation of free Ca2+ inside nerve terminals, similarly counteracted the effect of clonidine 10 nM. Whereas the alpha 2-adrenergic inhibition of the first e.j.p. in a train was unaffected, the inhibition of all successive e.j.p.s was gradually decreased. At 5 mM Ca2+ only the time-course of facilitation became faster, the decrease in alpha 2-adrenergic inhibition proceeded with the same pulse-dependent rate as at a normal external Ca2+ concentration, although from a lower initial level.(ABSTRACT TRUNCATED AT 250 WORDS)
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D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013324:Strontium / Q000494:pharmacology; D009435:Synaptic Transmission; D014649:Vas Deferens / Q000187:drug effects
D000631:Aminopyridines; D011942:Receptors, Adrenergic, alpha; D001464:Barium; D015761:4-Aminopyridine; D003000:Clonidine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D013324:Strontium