Functionally distinct muscarinic receptors on gastric somatostatin cells

The present study was designed to examine the mode of action of muscarinic agonists on somatostatin secretion in intact gastric tissues, i.e., mucosal segments from the fundus and antrum of rat and the isolated luminally perfused mouse stomach. Methacholine caused similar decreases in somatostatin secretion in segments from the fundus (35 +/- 3%; P less than 0.001) and antrum (35 +/- 2%; P less than 0.001) of rat stomach, and in whole mouse stomach (43 +/- 3%; P less than 0.001). The decrease was the net effect of a dominant inhibition and a lesser stimulation of somatostatin secretion. Pretreatment with the permeant derivative of the acetomethoxy ester form of the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM, 15 microM) caused a further decrease in methacholine-induced somatostatin secretion, implying that a stimulatory component existed that was mediated by intracellular calcium. Pretreatment with pertussis toxin (125 ng/ml) for 60 min converted the decrease in somatostatin secretion to an increase above basal levels. The increase induced by pretreatment with pertussis toxin was abolished by additional pretreatment with BAPTA/AM. Procaine (5 mM), which blocks release of calcium from intracellular stores, produced an effect on somatostatin secretion similar to that of BAPTA/AM. The results indicate that 1) methacholine exerts dual inhibitory and stimulatory effects on somatostatin cells of rat and mouse stomach, 2) the dominant effect is inhibitory and sensitive to pertussis toxin, and 3) a concurrent stimulatory effect, mediated by calcium, is unmasked after blockade of the inhibitory effect with pertussis toxin.

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Effect of catecholamines on somatostatin secretion by isolated perfused rat stomach

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1981.240.3.e274 ◽

1981 ◽

Vol 240 (3) ◽

pp. E274-E278

Author(s):

Y. Goto ◽

M. Berelowitz ◽

L. A. Frohman

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Inhibitory Effect ◽

Dependent Manner ◽

Rat Stomach ◽

Beta Adrenergic ◽

Somatostatin Secretion ◽

Adrenergic Mechanism ◽

Dose Dependent

The secretion of somatostatin-like immunoreactivity (SRIF-LI) by the isolated perfused rat stomach was studied in response to stimulation by catecholamines. Gastric SRIF-LI secretion was significantly stimulated in a dose-dependent manner by norepinephrine at 10(-6) and 10(-8) M, and the effect of norepinephrine (10(-8) M) was attenuated by the addition of propranolol (10(-6) M) but not of phentolamine (10(-6) M). SRIF-LI secretion was also stimulated by dopamine at concentrations of 10(-4) and 10(-6) M but not at 10(-8) M. The effect of dopamine (10(-6) M) was not altered by the addition of haloperidol (10(-4) to 10(-7)) or metoclopramide (10(-4) M), and bromocriptine (10(-6) M) was without effect on SRIF-LI secretion. These results suggest that gastric SRIF-LI secretion is stimulated by a beta-adrenergic mechanism and raise the possibility that gastric somatostatin contributes to the inhibitory effect of norepinephrine on gastric acid secretion.

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Neural regulation of gastrin and somatostatin secretion in rat gastric antral mucosa

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1987.253.6.g721 ◽

1987 ◽

Vol 253 (6) ◽

pp. G721-G725 ◽

Cited By ~ 2

Author(s):

M. L. Schubert ◽

G. M. Makhlouf

Keyword(s):

Electrical Stimulation ◽

Ussing Chamber ◽

Aluminum Foil ◽

Antral Mucosa ◽

Field Stimulation ◽

Rat Stomach ◽

Twofold Increase ◽

Somatostatin Secretion ◽

Preferential Activation ◽

Stimulation Of

A muscle-stripped mucosal sheet obtained from rat antrum was mounted in an Ussing chamber and used to examine the regulation of gastrin and somatostatin secretion by antral neurons. The neurons were activated pharmacologically with 1,1-dimethyl-4-phenylpiperazinium (DMPP) or electrically by field stimulation using aluminum foil electrodes layered over the edge of the mucosal sheet. Field stimulation caused an increase in gastrin and somatostatin secretion that was dependent on the strength of the stimulus (10-30 V). Field stimulation at 30 V, 10 Hz, 4 ms caused a sixfold increase in gastrin and a twofold increase in somatostatin secretion that were nearly abolished by tetrodotoxin (85-89% inhibition). Atropine partially inhibited the gastrin response (34 +/- 6%) but had no effect on the somatostatin response. DMPP caused lesser, though significant, increases in gastrin (166%) and somatostatin (83%) secretion that were nearly abolished by hexamethonium (84-91%) but were not significantly affected by atropine. The increase in somatostatin secretion caused by DMPP and field stimulation, as well as the resistance of gastrin and somatostatin secretion to atropine, was consistent with preferential activation of noncholinergic neurons at the stimulatory modalities used. The pattern and magnitude of gastrin and somatostatin response to pharmacological and electrical stimulation of antral neurons were similar to those previously observed in the vascularly perfused whole rat stomach.

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Pertussis toxin does not inhibit muscarinic-receptor-mediated phosphoinositide hydrolysis or calcium mobilization

Biochemical Journal ◽

10.1042/bj2270933 ◽

1985 ◽

Vol 227 (3) ◽

pp. 933-937 ◽

Cited By ~ 217

Author(s):

S B Masters ◽

M W Martin ◽

T K Harden ◽

J H Brown

Keyword(s):

Muscarinic Receptor ◽

Muscarinic Receptors ◽

Pertussis Toxin ◽

Inositol Phosphate ◽

Regulatory Protein ◽

Calcium Mobilization ◽

Phosphoinositide Hydrolysis ◽

Heart Cells ◽

Chick Heart ◽

Stimulation Of

Pertussis toxin was used to examine the role of the inhibitory guanine nucleotide regulatory protein, Ni, in muscarinic-receptor-mediated stimulation of phosphoinositide turnover and calcium mobilization. In cultured chick heart cells, pertussis-toxin treatment inhibited muscarinic-receptor-mediated attenuation of isoprenaline-stimulated cyclic AMP accumulation. This finding is consistent with the proposal that pertussis toxin blocks the capacity of Ni to couple muscarinic receptors to adenylate cyclase. In contrast, treatment of chick heart cells or 1321N1 human astrocytoma cells with pertussis toxin did not block muscarinic-receptor-mediated stimulation of phosphoinositide hydrolysis, as measured by [3H]inositol phosphate accumulation in the presence of Li+. Pertussis-toxin treatment also had little effect on basal and muscarinic-receptor-stimulated phosphatidylinositol synthesis, as measured by the incorporation of [3H]inositol into phosphatidylinositol. Activation of muscarinic receptors also enhances the rate of unidirectional 45Ca2+ efflux in 1321N1 cells; this response, like phosphoinositide hydrolysis, was not prevented by pertussis-toxin treatment. Our data suggest that muscarinic receptors are not coupled to phosphoinositide hydrolysis or calcium mobilization through Ni.

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Desensitization of α7 nicotinic receptors potentiated the inhibitory effect on M-current induced by stimulation of muscarinic receptors in rat superior cervical ganglion neurons

Journal of Neural Transmission ◽

10.1007/s00702-004-0260-6 ◽

2004 ◽

Vol 112 (9) ◽

pp. 1133-1148 ◽

Cited By ~ 4

Author(s):

X. Yin ◽

W. Cui ◽

G. Hu ◽

H. Wang

Keyword(s):

Muscarinic Receptors ◽

Superior Cervical Ganglion ◽

Nicotinic Receptors ◽

Inhibitory Effect ◽

M Current ◽

Cervical Ganglion ◽

Ganglion Neurons ◽

Stimulation Of

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066 Noradrenaline and acetylcholine inhibit sleep-promoting neurons of ventrolateral preoptic area through a local GABAergic circuit

SLEEP ◽

10.1093/sleep/zsab072.065 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A27-A28

Author(s):

Roberto De Luca ◽

Stefano Nardone ◽

Lin Zhu ◽

Elda Arrigoni

Keyword(s):

Muscarinic Receptors ◽

Inhibitory Action ◽

Preoptic Area ◽

Brain Slices ◽

Inhibitory Effect ◽

Gabaergic Neurons ◽

Optogenetic Stimulation ◽

Direct Inhibitory Effect ◽

Afferent Inputs ◽

Stimulation Of

Abstract Introduction The ventrolateral preoptic (VLPO) nucleus is a key area involved in the initiation and maintenance of sleep. During wakefulness, sleep-promoting galanin neurons in the VLPO are directly inhibited by arousal signals including noradrenaline and acetylcholine. We have found that while these neurotransmitters directly inhibit VLPO galanin neurons, they also activate GABAergic neurons in the VLPO that do not express galanin. We propose that when activated by monoaminergic and cholinergic inputs, these local VLPO GABAergic neurons provide an additional inhibition of the VLPO galanin sleep-promoting neurons. We tested this model in brain slices in mice. Methods We studied VLPO galanin neurons in mouse brain slices using patch-clamp recordings. We recorded from fluorescently labeled VLPO galanin neurons following the injection of a cre-dependent AAV encoding for mCherry, into the VLPO of Gal-cre mice. For the optogenetic studies we expressed channelrhodopsin-2 (ChR-2) in VLPO VGAT neurons and mCherry in galanin neurons by injecting a flp-dependent and a cre-dependent AAV encoding respectively for ChR2 and mCherry into the VLPO of VGAT-flp::Gal-cre mice. We photo-stimulated local GABAergic neurons and recorded from labeled VLPO galanin neurons. Noradrenaline, carbachol and receptor antagonists were bath-applied. Results Noradrenaline and carbachol inhibited VLPO galanin neurons by alpha-2 and muscarinic receptors and these effects were maintained in the presence of tetrodotoxin (TTX) indicating, as previously proposed, a direct inhibitory effect of noradrenaline and carbachol on VLPO galanin neurons. In addition, both noradrenaline and carbachol increased the frequency of spontaneous inhibitory post-synaptic currents (sIPSCs) of VLPO galanin neurons, suggesting an additional inhibitory action on VLPO galanin neurons. Finally, optogenetic stimulation of local VLPO GABAergic neurons produced short latency, TTX-resistant, opto-evoked IPSCs in VLPO galanin neurons. Both noradrenaline and carbachol increased the amplitude of these opto-evoked IPSCs by the activation of alpha-1 and muscarinic receptors. Conclusion Our results demonstrate that noradrenaline and acetylcholine inhibit VLPO galanin neurons directly and indirectly. Both noradrenaline and acetylcholine increase GABAergic afferent inputs to VLPO galanin neurons by activating local GABAergic neurons. We propose that during wakefulness this feedforward inhibition provides additional inhibition of VLPO galanin sleep-promoting neurons. Support (if any) NS091126 and HL149630

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Effect of substance P and neurokinin A on rat parietal cell function

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.4.g646 ◽

1990 ◽

Vol 259 (4) ◽

pp. G646-G654

Author(s):

W. Schepp ◽

J. Schmidtler ◽

C. Tatge ◽

V. Schusdziarra ◽

M. Classen

Keyword(s):

Substance P ◽

Parietal Cell ◽

Pertussis Toxin ◽

Cell Function ◽

Inhibitory Effect ◽

Parietal Cells ◽

Neurokinin A ◽

Cholinergic Stimulation ◽

Camp Production ◽

Stimulation Of

In enzymatically dispersed enriched (76%) rat parietal cells we studied the effect of substance P on acid sequestration as indirectly measured by [14C]aminopyrine accumulation. Substance P (10(-8)-10(-5) M) had no effect on basal [14C]aminopyrine accumulation. Yet, the peptide reduced the response to histamine and to the postreceptor agonists forskolin and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Inhibition by substance P followed noncompetitive kinetics and reduced stimulated parietal cell function by up to 45% at 10(-5) M. The antagonist [D-Pro2, D-Trp7,9]-substance P at 10(-5) M partly reversed the inhibitory effect of substance P. Cholinergic stimulation of [14C]aminopyrine accumulation was not reduced by substance P. Neurokinin A, another tachykinin that is structurally related to substance P, was of comparable potency and efficacy in reducing [14C]aminopyrine accumulation in response to histamine, forskolin, and DBcAMP. Inhibition of forskolin- or DBcAMP-induced [14C]aminopyrine accumulation persisted in the presence of 10(-5) M ranitidine. Inhibition by substance P and neurokinin A of the response to histamine was not sensitive to pertussis toxin. Both tachykinins failed to reduce histamine- and forskolin-stimulated cAMP production. Our data suggest that substance P and neurokinin A exert a direct effect on rat parietal cells. They attenuate histamine-stimulated acid sequestration at an intracellular step that is distal to the adenylate cyclase and that does not involve pertussis toxin-sensitive GTP-binding proteins.

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Linkage between somatostatin and acid secretion: evidence from use of pertussis toxin

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.256.2.g418 ◽

1989 ◽

Vol 256 (2) ◽

pp. G418-G422 ◽

Cited By ~ 5

Author(s):

M. L. Schubert ◽

J. Hightower ◽

G. M. Makhlouf

Keyword(s):

Adenylate Cyclase ◽

Acid Secretion ◽

Pertussis Toxin ◽

Somatostatin Receptors ◽

Inhibitory Effect ◽

Cellular Level ◽

Guanine Nucleotide Binding Protein ◽

Somatostatin Secretion ◽

Parallel Increase ◽

Guanine Nucleotide Binding

Pertussis toxin was used to examine the functional linkage between somatostatin and acid secretion and the mode of action of somatostatin at the cellular level in the isolated luminally perfused mouse stomach. Pretreatment of the stomach with pertussis toxin (125-1,250 ng/ml) for 60 min 1) caused a significant twofold increase in histamine-stimulated acid secretion (from 42 +/- 7 to 82 +/- 12 nmol/min; P less than 0.01) but not pentagastrin-stimulated secretion and 2) blocked the inhibitory effect of somatostatin on basal and histamine-stimulated acid secretion but not on pentagastrin-stimulated acid secretion. The ability of pertussis toxin to reverse selectively the inhibitory effect of somatostatin on histamine-stimulated acid secretion is consistent with the ability of pertussis toxin to inactivate a guanine nucleotide binding protein, which couples somatostatin receptors to inhibition of adenylate cyclase; histamine, but not gastrin, stimulates acid secretion via activation of adenylate cyclase. Secretagogue-stimulated acid secretion was accompanied by a parallel increase in somatostatin secretion that is largely determined by luminal acidity. The augmentation of histamine-stimulated acid secretion after treatment with pertussis toxin implied that the concomitant increase in somatostatin secretion is coupled to acid secretion and acts to attenuate it. The results confirm the role of gastric somatostatin as a paracrine regulator of acid secretion.

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Inhibitory effect of nociceptin on somatostatin secretion of the isolated perfused rat stomach

Regulatory Peptides ◽

10.1016/s0167-0115(02)00061-7 ◽

2002 ◽

Vol 107 (1-3) ◽

pp. 37-42 ◽

Cited By ~ 6

Author(s):

Florian Lippl ◽

Volker Schusdziarra ◽

Kerstin Huepgens ◽

Hans-Dieter Allescher

Keyword(s):

Inhibitory Effect ◽

Rat Stomach ◽

Somatostatin Secretion

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Pertussis toxin blocks the inhibitory effect of muscarinic cholinergic agonists on cyclic AMP accumulation and prolactin secretion in GH3 anterior-pituitary tumour cells

Biochemical Journal ◽

10.1042/bj2230145 ◽

1984 ◽

Vol 223 (1) ◽

pp. 145-149 ◽

Cited By ~ 11

Author(s):

B L Brown ◽

R J H Wojcikiewicz ◽

P R M Dobson ◽

A Robinson ◽

L I Irons

Keyword(s):

Cyclic Amp ◽

Pertussis Toxin ◽

Anterior Pituitary ◽

Pituitary Tumour ◽

Inhibitory Effect ◽

Prolactin Secretion ◽

Gh3 Cells ◽

Muscarinic Agonists ◽

Cyclic Amp Accumulation ◽

Muscarinic Cholinergic

The inhibition of prolactin secretion and cyclic AMP accumulation in GH3 cells by muscarinic agonists was blocked by preincubation of the cells with pertussis toxin (islet-activating protein). There was a lag of approx. 80 min in the onset of the effect on secretion. These results suggest that muscarinic agonists decrease prolactin secretion by inhibiting adenylate cyclase activity.

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