Contrasting Actions of Amino Acids, Acetylcholine, Noradrenaline and Leucine Enkephalin on the Excitability of Supraoptic Vasopressin-Secreting Neurons

Abstract

The preferential release of the neurohypophyseal hormones vasopressin and oxytocin by appropriate stimuli implies that neurons secreting each hormone receive different afferent connections and may therefore contain membrane receptors for different neurotransmitters. Since electrophysiological studies on rat supraoptic nucleus (SON) neurosecretory neurons suggest that the activated vasopressin-secreting neuron may be selectively identified by a phasic activity pattern, extracellular recordings were performed in pentobarbital anesthetized male Sprague-Dawley rats to compare the responses of 59 phasically-active SON neurosecretory cells to several neurotransmitter candidates endogenous to SON and applied by microiontophoresis. Among excitatory agents, most SON cells demonstrated a brisk depolarization to aspartate and glutamate; quiescent cells could also be induced into phasic activity by continuous application of either amino acid with low currents. During applications of acetylcholine and nicotine, phasically active neurons demonstrated elongated periods of continued activity, but without an increase in overall firing frequency, suggesting a possible mechanism for cholinergic enhancement of vasopressin release. In contrast, norepinephrine (NE) exerted an opposite action by either terminating a burst of activity prematurely or decreasing the number of action potentials per burst; some cells displayed a prolonged arrest of phasic activity for several minutes following NE applications. This mechanism of action could explain any inhibitory effect of NE on vasopressin secretion. We observed no apparent tachyphylaxis to repeated NE applications. GABA applications also terminated phasic activity prematurely, but cell firing resumed within seconds of removal of the application currents. Leucine enkephalin exerted a weak depressant action on the excitability of a small percentage of phasically-active SON neurons. For further comparison, we tested these agents on 18 continuously-active (possible oxytocin-secreting) SON neurosecretory neurons. Most of these neurons demonstrated changes in excitability similar to that noted on phasically-active cells; however, the duration of drug action seldom outlasted the period of its application. One exception was the observation that acetylcholine, but not nicotine, depressed the firing of a portion of the continuously-active SON neurosecretory cell population. These extracellular observations provide preliminary evidence of differences in the neuropharmacological properties of SON putative vasopressin- and oxytocin-secreting neurons that may be better clarified with detailed intracellular measurements.