Effect of gastric secretagogues on the formation of inositol phosphates in isolated gastric cells of the rat

Puurunen, Juhani; Schwabe, Ulrich

doi:10.1111/j.1476-5381.1987.tb11197.x

Cited by 19 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The recent hypothesis of Berridge & Irvine (1 984) suggests that inositol 1,4,5-trisphosphate formed from phosphatidylinositol 4,5bisphosphate upon receptor activation would act as the second messenger for the release of calcium ions. In fact, our recent findings suggest that the secretory action of acetylcholine and gastrin may be mediated via increased formation of inositol trisphosphate in the parietal cells (Puurunen & Schwabe 1987). Of special interest is the recent finding of Hollingsworth et al (1986) that adenosine analogues enhance the histamine Hl-receptor-mediated acumulation of inositol phosphates in guinea-pig cortical slices.…”

Section: Discussionmentioning

confidence: 69%

“…Adenylate cyclase activity was assayed as described by Jakobs et al (1 976) using parietal cell preparations which were immediately frozen with liquid nitrogen after the enrichment. The determination of the formation of 3H-labelled inositol phosphates was performed in a similar manner to that described by Berridge et al (1982Berridge et al ( & 1983 with the modifications described elswhere (Puurunen & Schwabe 1987). The assay of 3H-PIA binding to gastric cell membranes was made by the method described by Trost & Schwabe (1981).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Lack of Direct Effect of Adenosine on the Parietal Cell Function in the Rat

Puurunen

Ruoff²,

Schwabe

1987

Pharmacology & Toxicology

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 69%

mentioning

confidence: 99%

Lack of Direct Effect of Adenosine on the Parietal Cell Function in the Rat

Puurunen

Ruoff²,

Schwabe

1987

Pharmacology & Toxicology

Self Cite

View full text Add to dashboard Cite

“…Muscarinic-receptor-mediated stimulation of acid, pepsinogen and mucous secretion by rat gastric cells is thought to involve the phosphoinositide second messenger system (Soll, 1981;Chew and Brown, 1986;Pfeiffer et al, 1986Pfeiffer et al, , 1988Puurunen and Schwabe, 1987;Seidler and Pfeiffer, 1991). In this system, receptor-mediated activation of phospholipase C results in the cleavage of phosphatidylinositol 4,5-trisphosphate into inositol trisphosphate and diacylglycerol (Berridge, 1987;Nishizuka, 1988).…”

Section: Introductionmentioning

confidence: 99%

Characterization of γ- and δ-subunits of Ca2+/calmodulin-dependent protein kinase II in rat gastric mucosal cell populations

Mayer

Möhlig

Seidler

et al. 1994

Biochemical Journal

View full text Add to dashboard Cite

We searched for the occurrence of a Ca2+/calmodulin-dependent protein kinase in rat gastric cell types as a likely member in the chain of gastrin- and muscarinic-receptor-mediated signal transmission. A Ca(2+)- and calmodulin-dependent phosphorylation of major 50, 60 and 100 kDa substrates was observed in parietal cell cytosol and a major 60 and 61 kDa protein doublet was found to bind 125I-calmodulin in 125I-calmodulin-gel overlays. A specific substrate of the multifunctional Ca2+/calmodulin-dependent protein kinase II, autocamtide II, was phosphorylated in a calmodulin-dependent manner. The specific inhibitor of this enzyme, KN-62, antagonized protein kinase activity. RNA extracted from gastric mucosal cells was shown to contain sequences of the gamma- and delta- but not alpha- and beta-subunits of the calmodulin-dependent kinase II, and mRNA of both subtypes was demonstrated in highly purified parietal, chief and mucous cells. A calmodulin-dependent kinase II composed of gamma- and delta-subunits is a likely mediator of Ca(2+)-dependent signal transmission in these populations of gastric cells.

show abstract

“…However, approximately 250/0 of the binding sites in mucosa had low affinity for HHSiD, suggesting the presence of a second subtype of muscarinic receptors. Muscarinic non-Ml receptors in enriched gastric parietal ceIls (10) activate the phosphoinositol system, which probably provides the second messengers activating acid secretion (10)(11)(12)(13). This model system allows a characterization of the muscarinic receptor sub type iqvolved in acid secretion by both functional and radioligand binding studies (14,15).…”

mentioning

confidence: 99%

Muscarinic receptors mediating acid secretion in isolated rat gastric parietal cells are of M3 type

et al. 1990

View full text Add to dashboard Cite

Five sub types of muscarinic receptors have been identified by pharmacological and molecular biological methods. The muscarinic receptor subtype mediating acid secretion at the level of the parietal cell was unknown. Therefore, this study was performed to characterize muscarinic receptors on rat gastric parietal cells using the 3 subtype-selective antagonists hexahydrosiladifenidol and silahexocyclium, which have high affinity for glandular M3 subtypes, and AF-DX 116, which has high affinity to cardiac M2 receptors. The affinity of these antagonists was determined by radio ligand binding experiments. In addition, their inhibitory potency on carbachol-stimulated inositol phosphate production was investigated. Inhibition of carbachol-stimulated aminopyrine uptake was used as an indirect measure of proton production. Hoth M3 antagonists, hexahydrosiladifenidol and silahexocyclium, had nanomolar affinities for parietal cell muscarinic receptors and potently antagonized inositol phosphate production with nanomolar Ki values. Silahexocyclium similarly antagonized aminopyrine accumulation while hexahydrosiladifenidol behaved as a noncompetitive antagonist. AF-DX 116 was a low-affinity ligand and a weak competitive antagonist at parietal-cell mus carinic receptors. It was concIuded that muscarinic M3 receptors mediate acid secretion probably by activation of the phosphoinositide second messenger system in rat gastric parietal cells. M uscarinic cholinergic receptors have originaIly been subclassified by their different affinities for the nonclassical muscarinic antagonist pirenzepine (1,2), which has high affinity for neuronal Ml and low affinity for non-Ml receptors. Based on molecular cloning of muscarinic receptors, there is now evidence for 5 different subclasses (3-5). Antagonists such as AF-DX 116 (6) were more potent in antagonizing muscarinic actions in cardiac M2 than in smooth muscle M3 (previously termed M2ß) receptors. Compounds such as hexahydrosiladifenidol (HHSiD) and silahexocyclium (SiHC] possess 10-30-fold higher affinity for smooth muscle and glandular M3 than cardiac M2-receptor subtypes (7,8).We have previously analyzed the radioligand binding properties of muscarinic M2 receptors in homogenates of porcine gastric mucosa (9). These data showed that HHSiD had high affinity (Kd = 3 nM) to the majority of mucosal receptors while AF-DX 116 had low affinity (Kd = 3000 nM) compatible with the M3 subtype. However, approximately 250/0 of the binding sites in mucosa had low affinity for HHSiD, suggesting the presence of a second subtype of muscarinic receptors. Muscarinic non-Ml receptors in enriched gastric parietal ceIls (10) activate the phosphoinositol system, which probably provides the second messengers activating acid secretion (10-13). This model system allows a characterization of the muscarinic receptor sub type iqvolved in acid secretion by both functional and radioligand binding studies (14,15). The aim of the present study was to characterize the muscarinic receptor subtype involved in the break...

show abstract

Effect of gastric secretagogues on the formation of inositol phosphates in isolated gastric cells of the rat

Abstract: 8 We suggest that the hydrolysis of inositol phospholipids may be involved in the signal transduction mechanism by which the activation of the muscarinic and gastrin receptors on the parietal cells leads to Ca2" mobilization and the stimulation of hydrogen ion secretion.

Cited by 19 publications

References 31 publications

Lack of Direct Effect of Adenosine on the Parietal Cell Function in the Rat

Lack of Direct Effect of Adenosine on the Parietal Cell Function in the Rat

Characterization of γ- and δ-subunits of Ca2+/calmodulin-dependent protein kinase II in rat gastric mucosal cell populations

Muscarinic receptors mediating acid secretion in isolated rat gastric parietal cells are of M3 type

Contact Info

Product

Resources

About