Showing papers by "Gang Wang published in 2000"
TL;DR: Evidence is considered 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, which could explain the patterns of AVP release observed during physiological stimulation in vivo.
Abstract: 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+ (Kca) 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 Kca current in a dose-dependent manner. Thus, intracellular and extracellular ATP exert opposite effects on the type II Kca channel of neurohypophysial terminals. Furthermore, ATP opens P2±2 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.
23 citations
TL;DR: It is concluded that agmatine is a neurotransmitter in AVP neurons of PVH and SON, wherein it functions as a paracrine/autocrine inhibitor of AVP release by blocking Ca ++ channels and may regulate neurally integrated release of this important hormone, regulating its cardiovascular and renal functions.
Abstract: 20 Agmatine (decarboxylated arginine), an organic cation, endogenous ligand at imidazoline (I-) and α 2 -adrenergic receptors, antagonist of NMDA receptors and inhibitor of nitric oxide synthase, may be a novel neurotransmitter in mammalian CNS (Reis and Regunathan, TIPS, 2000). To further establish a cellular function of agmatine we investigated whether it is expressed in, and regulates the function of, magnocellular neurons of the hypothalamic paraventricular (PVH)/supraoptic (SON) nuclei in rat. By LM, agmatine-like immunoreactivity (Ag-LI) was present in virtually all magnocellular PVH and SON neurons, where it co-localized with arginine vasopressin (AVP) and oxytocin (OXY). By EM, Ag-LI was present in large dense core vesicles in neurohypophysial nerve terminals (NNTs), known storage sites of the peptides. NNTs acutely isolated from adult rats were dispersed and voltage-activated Na + , K + , and Ca ++ currents recorded in whole terminals in amphotericin B perforated-patches. Agmatine (40-120 uM) did not affect the voltage-dependent, TTX-sensitive inward Na + , the 4-AP-sensitive, transient outward A-type K + current, or the sustained, Ca ++ -activated, maxi-conductance K + currents. In ∼ 60% of terminals 40 uM agmatine immediately, dose-dependently and reversibly blocked whole cell Ca ++ currents evoked by 10 mM Ca ++ with an IC 50 ∼ 5 uM. Agmatine blocked the depolarization-induced release of AVP from isolated NNTs. We conclude that agmatine: (a) is co-stored with neuropeptides in hypothalamo-neurohypophysial neurons, and (b) inhibits pre-synaptic Ca ++ channels to (c) inhibit release of AVP. Agmatine is a neurotransmitter in AVP neurons of PVH and SON, wherein it functions as a paracrine/autocrine inhibitor of AVP release by blocking Ca ++ channels. Agmatine may regulate neurally integrated release of this important hormone, regulating its cardiovascular and renal functions.
1 citations