Excitatory versus inhibitory modulation by ATP of neurohypophysial terminal activity in the rat
Department of Physiology and Neuroscience Program
Adenosine Triphosphate; Animals; Calcium; Neural Inhibition; Pituitary Gland, Posterior; Potassium Channels; Presynaptic Terminals; Rats
Life Sciences | Medicine and Health Sciences
Much is now known about the electrophysiological properties of the magnocellular neurones of the hypothalamus. Oxytocin neurones are characterized by an intermittent high frequency discharge during suckling that leads to the pulsatile release of oxytocin into the blood and to subsequent milk ejection. Vasopressin neurones are characterized by their asynchronous phasic activity (bursting) during maintained vasopressin release and the subsequent regulation of water balance. In both cases, it is the clustering of spikes, albeit with different time courses for each peptide, that facilitates hormone release. The mechanism underlying this differential facilitation is one of the major unanswered questions in neuroendocrinology. This paper considers recent evidence that indicates that ATP, co-secreted with vasopressin and oxytocin, may play a key role in the regulation of stimulus-secretion coupling in the neurohypophysis. The activity of the type (II) Ca2+-activated K+ (K(Ca)) channel found in the nerve terminals was significantly increased in the presence of ATP on the cytoplasmic side of the channel. Extracellular ATP, in contrast, inhibited the type II K(Ca) current in a dose-dependent manner. Thus, intracellular and extracellular ATP exert opposite effects on the type II K(Ca) channel of neurohypophysial terminals. Furthermore, ATP opens P2X2 channels to increase intracellular [Ca2+] in the nerve terminals and subsequent arginine vasopressin (AVP) release. In contrast, adenosine, acting via A1 receptors, specifically inhibits only the N-type Ca2+ channel, thus decreasing neuropeptide release. These multiple, conflicting effects of ATP and its metabolite adenosine could explain the patterns of AVP release observed during physiological stimulation in vivo.
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Citation: Exp Physiol. 2000 Mar;85 Spec No:67S-74S.
Lemos, Jose R. and Wang, Gang, "Excitatory versus inhibitory modulation by ATP of neurohypophysial terminal activity in the rat" (2000). Open Access Articles. 561.