Summary
Excitatory junction potentials (e j.ps; intracellular electrodes) and excitatory junction currents (e.j.cs; extracellular electrodes) elicited by stimulation (20 pulses at 1 Hz every minute) of the hypogastric nerve trunk were recorded from guinea-pig isolated vas deferens.
Intracellular recording. At a variety of stimulation intensities, bath-applied yohimbine (0.1–1 μmol/l) did not change the first one to three e j.ps in a train but increased the amplitude of subsequent e j.ps. The effect of yohimbine was abolished in tissues from reserpinepretreated guinea pigs. Bath-applied desipramine (0.1 μmol/l) diminished the amplitude of all but the first one to three e j.ps in a train. - Extracellular recording. Yohimbine (0.1–1 μmol/l), when applied locally through the recording suction electrode, increased the number of e.j.cs per given number of stimuli, i. e., enhanced the probability of occurrence of e.j.cs. When desipramine (0.1 μmol/l) was present both in the bath and in the recording electrode, the probability of the occurrence of e.j.cs was decreased. In the presence of desipramine, yohimbine (0.1–1 μmol/l) increased the number of e j.cs even more markedly. Neither the nerve terminal impulse nor the number of spontaneous e j.cs was changed by yohimbine. A mixture of tetraethylammonium (2 mmol/l) and 4-aminopyridine (0.2 mmol/l), when applied locally, both increased the number of e.j.cs and changed markedly the shape of the nerve terminal impulse.
These experiments demonstrate presynaptic α2-autoinhibition at a high degree of resolution, i. e., when the intermittent release of transmitter from only a few varicosities along a single terminal axon is monitored by the e j.c. α2-Autoinhibition is not due to a depression of impulse conduction but to a depression of stimulus-secretion coupling in varicosities reached by the impulse. Taken together with the low probability of transmitter release at the level of individual varicosities, the results support the idea of lateral inhibition by noradrenaline released from distant varicosities rather than inhibition due to noradrenaline released from the same varicosity. The mode of action of yohimbine differs from that of K+ channel blocking agents.
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Brock, J.A., Cunnane, T.C., Starke, K. et al. α2-Adrenoceptor-mediated autoinhibition of sympathetic transmitter release in guinea-pig vas deferens studied by intracellular and focal extracellular recording of junction potentials and currents. Naunyn-Schmiedeberg's Arch Pharmacol 342, 45–52 (1990). https://doi.org/10.1007/BF00178971
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DOI: https://doi.org/10.1007/BF00178971