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At least 595 records · Page 33Linked to original sources
PubMed1999

Evaluation of quantal neurosecretion from evoked and miniature postsynaptic responses by deconvolution method.

A new deconvolution algorithm has been developed for evaluation of quantal content and its variability at high-output synapses. The algorithm derives the distribution of the number of neurosecretory quanta released in a trial (M) from the measured sizes of evoked postsynaptic responses. The deconvolution employs the distribution of quantal sizes obtained by measuring sizes of miniature postsynaptic responses. The distribution of quantal content M is derived by ridge regression method from the distributions of sizes of the responses and of quantal sizes. The deconvolution method was applied to postsynaptic responses from the excitory innervation of lobster dactyl opener muscle obtained by focal extracellular recordings. The obtained solution (distribution of M) had six to eight components and was stable. The method was tested by the analysis of simulated multiquantal responses. For the simulated responses, the ridge regression solution reproduced the imposed distribution of M within the limits of the calculated confidence intervals. To further test the algorithm, the distribution of M at a low-output synapse was obtained both by deconvolution method and by the method of direct quantal counts. The results of these two methods were found to be in a very good agreement.

Action Potentials↗
PubMed1969

Correlated effects of ecdysone and neurosecretion in puparium formation (pupariation) of flies.

A neurohormone accelerates the formation and tanning of the fly puparium in the presence of ecdysone. When larvae of Phormia regina are divided by ligation into two parts before the critical period, the hind part remains untanned, unless injected with blood from a pupariating larva. This confirms earlier observations and is in contrast to recent data with another genus. When Sarcophaga bullata larvae are ligated after the critical period, the anterior part starts to tan about two hours before the posterior part. Injecting neurosecretory material from the brain, the pars intercerebralis, or the corpora cardiaca of S. bullata, or from the brain or c. cardiaca of Periplaneta or Pyrrhocoris into the posterior part induces it to tan before the anterior part. Injection of the same material into normal larvae after the critical period similarly accelerates puparium formation and onset of tanning. Injection of ecdysone or ecdysterone does not have these effects. Thus, the neurosecretory material does not act by causing the release of ecdysone from the ring gland and its function is different from that of the classical brain ("activating") hormone. When injected before the critical period together with ecdysone it potentiates the effect of ecdysone. It is suggested that its biological significance is to coordinate puparial contraction and tanning.

Journal Article↗
PubMed1990

K+ channel openers activate brain sulfonylurea-sensitive K+ channels and block neurosecretion.

Vascular K+ channel openers such as cromakalim, nicorandil, and pinacidil potently stimulate 86Rb+ efflux from slices of substantia nigra. This 86Rb+ efflux is blocked by antidiabetic sulfonylureas, which are known to be potent and specific blockers of ATP-regulated K+ channels in pancreatic beta cells, cardiac cells, and smooth muscle cells. K0.5, the half-maximal effect of the enantiomer (-)-cromakalim, is as low as 10 nM, whereas K0.5 for nicorandil is 100 nM. These two compounds appear to have a much higher affinity for nerve cells than for smooth muscle cells. Openers of sulfonylurea-sensitive K+ channels lead to inhibition of gamma-aminobutyric acid release. There is an excellent relationship between potency to activate 86Rb+ efflux and potency to inhibit neurotransmitter release.

Animals↗
PubMed1997

Dependence of intracellular signaling and neurosecretion on phospholipase D activation in immortalized gonadotropin-releasing hormone neurons.

The excitability of gonadotropin-releasing hormone (GnRH) neurons is essential for episodic neuropeptide release, but the mechanism by which electrical activity controls GnRH secretion is not well characterized. The role of phospholipase D (PLD) in mediating the activity-dependent secretory pathway was investigated in immortalized GT1 neurons, which both secrete GnRH and express GnRH receptors. Activation of these Ca2+-mobilizing receptors was associated with transient hyperpolarization of GT1 cells, followed by sustained firing of action potentials. This was accompanied by an increase in PLD activity, as indicated by elevated phosphatidylethanol (PEt) production. GnRH-induced PEt production was reduced by inhibition of phospholipase C-dependent phosphoinositide hydrolysis by U73122 and neomycin, suggesting that signaling from phospholipase C led to activation of PLD. The intermediate role of protein kinase C (PKC) in this process was indicated by the ability of phorbol 12-myristate 13-acetate to induce time- and dose-dependent increases in PEt and diacylglycerol, but not inositol trisphosphate, and by reduction of GnRH-induced PEt accumulation in PKC-depleted cells. Consistent with the role of action potential-driven Ca2+ entry in this process, agonist-induced PLD activity was also reduced by nifedipine and low extracellular Ca2+. Inhibition of the PLD pathway by ethanol and propranolol reduced diacylglycerol production and caused a concomitant fall in GnRH release. These data indicate that voltage-gated Ca2+ entry and PKC act in an independent but cooperative manner to regulate PLD activity, which contributes to the secretory response in GT1 cells. Thus, the electrical activity of the GnRH-secreting neuron participates in the functional coupling between GnRH receptors and PLD pathway.

Calcium↗
PubMed2006

Essential role of G protein-gated inwardly rectifying potassium channels in gonadotropin-induced regulation of GnRH neuronal firing and pulsatile neurosecretion.

Activation of the luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor (LHR) in cultured hypothalamic cells and immortalized GnRH (gonadotropin-releasing hormone) neurons (GT1-7 cells) transiently stimulates and subsequently inhibits cAMP production and pulsatile GnRH release. The marked and delayed impairment of cAMP signaling and episodic GnRH release in GT1-7 cells is prevented by pertussis toxin (PTX). This, and the LH-induced release of membrane-bound Galpha(s) and Galpha(i3) subunits, are indicative of differential G protein coupling to the LHR. Action potential (AP) firing in identified GnRH neurons also initially increased and then progressively decreased during LH treatment. The inhibitory action of LH on AP firing was also prevented by PTX. Reverse transcriptase-PCR analysis of GT1-7 neurons revealed the expression of G protein-gated inwardly rectifying potassium (GIRK) channels in these cells. The LH-induced currents were inhibited by PTX and were identified as GIRK currents. These responses indicate that agonist stimulation of endogenous LHR expressed in GnRH neurons activates GIRK channels, leading to suppression of membrane excitability and inhibition of AP firing. These findings demonstrate that regulation of GIRK channel function is a dominant factor in gonadotropin-induced abolition of pulsatile GnRH release. Furthermore, this mechanism could contribute to the suppression of pituitary function during pregnancy.

Action Potentials↗
PubMed2002

Glycerotoxin from Glycera convoluta stimulates neurosecretion by up-regulating N-type Ca2+ channel activity.

We report here the purification of glycerotoxin from the venom of Glycera convoluta, a novel 320 kDa protein capable of reversibly stimulating spontaneous and evoked neurotransmitter release at the frog neuromuscular junction. However, glycerotoxin is ineffective at the murine neuromuscular junction, which displays a different subtype of voltage- dependent Ca(2+) channels. By sequential and selective inhibition of various types of Ca(2+) channels, we found that glycerotoxin was acting via Ca(v)2.2 (N-type). In neuroendocrine cells, it elicits a robust, albeit transient, influx of Ca(2+) sensitive to the Ca(v)2.2 blockers omega-conotoxin GVIA and MVIIA. Moreover, glycerotoxin triggers a Ca(2+) transient in human embryonic kidney (HEK) cells over-expressing Ca(v)2.2 but not Ca(v)2.1 (P/Q-type). Whole-cell patch-clamp analysis of Ca(v)2.2 expressing HEK cells revealed an up-regulation of Ca(2+) currents due to a leftward shift of the activation peak upon glycerotoxin addition. A direct interaction between Ca(v)2.2 and this neurotoxin was revealed by co-immunoprecipitation experiments. Therefore, glycerotoxin is a unique addition to the arsenal of tools available to unravel the mechanism controlling Ca(2+)-regulated exocytosis via the specific activation of Ca(v)2.2.

Animals↗
PubMed1988

Role of substance P and neurotensin in the regulation of neurosecretion and vascular responsiveness in hypertension.

The purpose of the present study was to investigate the effects of vasoactive neuropeptides, such as substance P or neurotensin, on vascular adrenergic neurotransmission in hypertension. In perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR), we examined the effects of substance P and neurotensin on vascular responsiveness and noradrenaline release from the sympathetic nerve endings. Stimulation-evoked noradrenaline release and pressor responses were inhibited by substance P and neurotensin. In SHR, the noradrenaline release and pressor responses during electrical nerve stimulation were significantly greater than in Wistar-Kyoto rats (WKY). The inhibitory effects of these responses by substance P and neurotensin were attenuated in SHR compared with WKY. These results showed that substance P and neurotensin could affect the presynaptic site of the blood vessels and cause a decrease in electrically stimulated noradrenaline release from the vascular adrenergic neurons. The reduction of noradrenaline release and pressor responses by substance P and neurotensin in SHR might suggest insufficient regulation of the vascular adrenergic transmission by these vasoactive peptides in hypertension.

Animals↗
PubMed1986

Human fetal hypothalamic GnRH neurosecretion: dopaminergic regulation in vitro.

An in-vitro perifusion system was used to investigate GnRH release from fetal (21-23 weeks gestation) human hypothalami in response to dopamine (DA) and the DA receptor antagonist haloperidol. Administration of 1 mumol/l DA during five perifusions in which 1 mumol/l haloperidol was added to the medium failed to alter basal GnRH release. In contrast DA evoked a rapid and sustained 95.8 +/- 20.3% increase (P less than 0.01) in GnRH release during five matching perifusions with medium containing the alpha-adrenergic antagonist phentolamine. While exposure to 0.01 mumol/l DA failed to alter basal GnRH release during three perifusions, 0.1 mumol/l DA elicited a 145.7 +/- 65.2% increase (P less than 0.05) in GnRH release in three matching perifusions, indicating a dose-dependent effect. These studies demonstrate that DA can stimulate in-vitro release of GnRH from the mid-gestation fetal human hypothalamus by a DA receptor mediated mechanism.

Dopamine↗
PubMed1992

Tunicamycin Dissociates Depolarization-induced Calcium Entry From Transmitter Release. Involvement of Glycosylated Protein(s) in the Process of Neurosecretion in PC-12 Cells.

The process of regulated secretion in PC-12 cells is tightly coupled to calcium entry, which is absolutely dependent on extracellular Ca2+([Ca2+]ex). Tunicamycin treatment of the cells dissociated depolarization-triggered Ca2+ influx from depolarization (high K+)-induced transmitter release into two distinct and independent phases. Deplarization-evoked Ca2+ influx was not affected by tunicamycin treatment (1 microg/ml, 72 h), whereas depolarization-evoked transmitter release was strongly inhibited (> 60%), suggesting at least a two-step process, and the participation of glycosylated protein(s) in the actual fusion/secretion step. Similarly, bradykinin-mediated transmitter release was linearly related to and absolutely dependent on Ca2+ entry, and was inhibited by tunicamycin treatment (> 80%), whereas bradykinin-evoked Ca2+ entry was not impaired, indicating that glycosylated protein(s) are essential for bradykinin-evoked release at a step subsequent to Ca2+ influx. The heavily glycosylated alpha2 subunit of the dihydropyridine-sensitive channel, which was used to monitor tunicamycin inhibition of glycosylation, was not expressed in the tunicamycin-treated cells, as shown by Western blot analysis. This observation allowed us to conclude that the alpha1 subunit of the heteromeric dihydropyridine voltage-sensitive Ca2+ channel, which is responsible for Ca2+ entry, is also fully functional when not assembled with its corresponding alpha2 subunit. The molecular properties of the alpha2 subunit, whose role in the complex structure of the channel is not yet understood, are shown for the first time for the L-type Ca2+ channel of PC-12 cells. Similar to cardiac and skeletal muscle cells, the alpha2 subunit appears to be a glycosylated polypeptide of molecular weight 170 kD and to display a characteristic mobility shift to 140 kD under reducing conditions.

Journal Article↗
PubMed2006

NMDA receptors trigger neurosecretion of 5-HT within dorsal raphe nucleus of the rat in the absence of action potential firing.

Activity and calcium-dependent release of neurotransmitters from the somatodendritic compartment is an important signalling mechanism between neurones throughout the brain. NMDA receptors and vesicles filled with neurotransmitters occur in close proximity in many brain areas. It is unknown whether calcium influx through these receptors can trigger the release of somatodendritic vesicles directly, or whether postsynaptic action potential firing is necessary for release of these vesicles. Here we addressed this question by studying local release of serotonin (5-HT) from dorsal raphé nucleus (DRN) neurones. We performed capacitance measurements to monitor the secretion of vesicles in giant soma patches, in response to short depolarizations and action potential waveforms. Amperometric measurements confirmed that secreted vesicles contained 5-HT. Surprisingly, two-photon imaging of DRN neurones in slices revealed that dendritic calcium concentration changes in response to somatic firing were restricted to proximal dendritic areas. This implied that alternative calcium entry pathways may dominate the induction of vesicle secretion from distal dendrites. In line with this, transient NMDA receptor activation, in the absence of action potential firing, was sufficient to induce capacitance changes. By monitoring GABAergic transmission onto DRN 5-HT neurones in slices, we show that endogenous NMDA receptor activation, in the absence of postsynaptic firing, induced release of 5-HT, which in turn increased the frequency of GABAergic inputs through activation of 5-HT(2) receptors. We propose here that calcium influx through NMDA receptors can directly induce postsynaptic 5-HT release from DRN neurones, which in turn may facilitate GABAergic input onto these cells.

Action Potentials↗
PubMed1993

Unbiased estimates of quantal release parameters and spatial variation in the probability of neurosecretion.

A procedure was developed for dealing with two problems that have impeded the use of quantal parameters in studies of transmitter release. The first, involving temporal and spatial biasing in the estimates for the number of functional release sites (n) and probability of release (p), was addressed by reducing temporal variance experimentally and calculating the bias produced by spatial variance in p (var(s)p). The second, involving inaccuracies in the use of nerve-evoked endplate potentials (EPPs), was circumvented by using only miniature EPPs (MEPPs). Intracellular recordings were made from isolated frog cutaneous pectoris, after decapitation and pithing of the animals, and the concentration of K+ ([K+]) was raised to 10 mM to increase the level of transmitter release. The number of quanta released (m) by the EPP was replaced by the number of MEPPs in a fixed time interval (bin), and 500 sequential bins used for each quantal estimate. With the use of 50-ms bins, estimates for var(s)p were consistently negative. This was due to too large a bin (and introduction of undetected temporal variance) because the use of smaller bins (5 ms) produced positive estimates of var(s)p. Increases in m, n, and p but not var(s)p were found in response to increases in [K+] or [Ca2+]/[Co2+]. La3+ (20 microM) produced increases in m and n, which peaked after 20 min and declined toward zero. There were also large increases in p and var(s)p, which peaked and declined only to initial control values. The increase in var(s)p was presumed to reflect La(3+)-induced release of Ca2+ from intracellular organelles. The results suggest that this approach may be used to obtain unbiased estimates of n and p and that the estimates of var(s)p may be useful for studying Ca2+ release from intraterminal organelles.

Animals↗
PubMed2001

Galanin-like peptide mRNA in neural lobe of rat pituitary. Increased expression after osmotic stimulation suggests a role for galanin-like peptide in neuron-glial interactions and/or neurosecretion.

Galanin-like peptide (GALP) was recently identified in the porcine hypothalamus, pituitary gland and gut, and has reported selectivity for the GalR2, c.f. the GalR1 receptor. GALP cDNAs have been cloned from pig, rat and human, and GALP mRNA expression is restricted to the arcuate nucleus in normal rat brain. This study examined the regional and cellular distribution of GALP mRNA in the rat pituitary gland, and subsequently determined the effect of osmotic stimulation on GALP transcript levels. GALP mRNA was not detected in the anterior or intermediate lobes, but moderate levels of GALP mRNA were present in the neural (posterior) lobe, in presumed pituicytes, of normal male and female rats. Osmotic stimulation by dehydration or salt loading produced a time-dependent increase in GALP mRNA levels in the neural lobe. Thus, dehydration for 4 days increased GALP mRNA 40-fold, while salt loading for 4, 7 or 10 days increased GALP levels 14-, 21- and 25-fold, respectively (p < or = 0.001). Levels of vasopressin (VP) mRNA in the neural lobe were also increased by these treatments, consistent with previous reports. Galanin (GAL) and GalR2 receptor mRNAs were not detected in the neural lobe, under normal or osmotic stimulation conditions. In addition, GALP mRNA levels in the arcuate nucleus were not altered in dehydrated or salt-loaded rats; and GALP mRNA was not detected in magnocellular neurons of the supraoptic or paraventricular nucleus, despite the characteristic up-regulation of VP and GAL mRNA in these cells. In view of the established anatomy and function of VP/oxytocin neurons in the hypothalamo-neurohypophysial system and the role played by pituicytes in their regulation, the likely synthesis/release of GALP by these specialized astrocytes strongly suggests a role for this novel peptide in regulation of pituicyte morphology/function and/or neurohormone release.

Animals↗
PubMed1987

Neurosecretion of human hypothalamic immunoreactive beta-endorphin: in vitro regulation by dopamine.

An in vitro perifusion system was used to investigate immunoreactive beta-endorphin (beta-END-I) release from adult human hypothalami in response to dopamine (DA) and the DA receptor antagonist haloperidol (HAL). Administration of a 1 microM pulse of DA consistently elicited a mean (+/- SE) 88 +/- 9% increase (p less than 0.05, n = 5) in beta-END-I release, whereas 1 microM HAL had no effect. Administration of 1 microM DA during three perifusions in which 1 microM HAL was added to the medium failed to alter basal beta-END-I release. In contrast, DA did evoke an acute 230 +/- 31% increase (p less than 0.05) in beta-END-I release during three matching perifusions with medium containing the alpha-adrenergic antagonist phentolamine. These studies demonstrate that DA can stimulate in vitro release of beta-END-I from the adult human hypothalamus by a DA receptor mediated mechanism.

Adult↗
PubMed1986

Gonadotropin-releasing hormone neurosecretion in the human hypothalamus: in vitro regulation by dopamine.

An in vitro perifusion system was used to investigate GnRH release from adult human hypothalami in response to dopamine (DA) and the DA receptor antagonist haloperidol (HAL). Administration of a 1-microM pulse of DA consistently elicited a mean +/- SE 218 +/- 59% increase (P less than 0.05; n = 5) in GnRH release, whereas 1 microM HAL had no effect. Administration of 1 microM DA during three perifusions in which 1 microM HAL was added to the medium failed to alter basal GnRH release. In contrast, DA did evoke an acute 98 +/- 39% increase (P less than 0.06) in GnRH release during three matching perifusions with medium containing the alpha-adrenergic antagonist phentolamine. These studies demonstrate that DA can stimulate in vitro release of GnRH from the adult human hypothalamus by a DA receptor-mediated mechanism.

Adult↗