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Biomedical subjects

I M Modlin

Publications and source records attributed to I M Modlin.

At least 73 records · Page 4Linked to original sources
PubMed1996

rab3D protein is a specific marker for zymogen granules in gastric chief cells of rats and rabbits.

BACKGROUND & AIMS: Pepsinogen secretion from gastric chief cells requires a series of intracellular vesicle interactions. The final step of exocytosis involves fusion of secretory granules with the plasmalemma, culminating in the release of the digestive enzyme pepsinogen into the lumina of gastric glands. A group of specialized proteins tht confer membrane recognition, targeting, and fusion events are involved in regulated exocytosis. The aim of this study was to examine the distribution of rab3D, a low-molecular-weight guanosine 5'-triphosphate-binding protein, in gastric chief cells. METHODS: rab3D immunoreactivity was evaluated by Western blot analysis and by immunocytochemical studies at both confocal and electron-microscopic levels. RESULTS: rab3D immunoreactivity was specifically localized to the secretory granules in chief cells. Double labeling of gastric glands with rab3D and pepsinogen antibodies confirmed rab3D immunoreactivity localization to chief cells but not acid-secreting parietal cells. Immunoelectron microscopy revealed a near exclusive localization of the rab3D-like protein to the cytoplasmic face of the zymogen granules. After short-term stimulation consequent to feeding, rab3D immunoreactivity appeared to relocate from an apical region of duct cells to an unidentified cytoplasmic compartment. CONCLUSIONS: The localization and redistribution of the rab3D-like protein in the chief cell suggests that it may play an important role in regulated exocytosis.

Animals↗
PubMed1996

Neurohormonal modulation of rat enterochromaffin-like cell histamine secretion.

BACKGROUND & AIMS: Gastric mucosal cells and nerve terminals contain at least acetylcholine, adrenergic agents, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, serotonin, gamma-amino-butyric acid, neurokinins A and B, neurotensin, neuropeptide Y, peptide YY, gastrin-releasing peptide, somatostatin, and [Met5]enkephalin. Although some of these agents have been implicated as regulators of gastric acid secretion, their site and mechanism of action is not well understood. The aim of this study was to investigate whether local gastric neurotransmitters modulate acid secretion by regulating basal and gastrin-driven enterochromaffin-like (ECL) cell histamine release. METHODS: The effects of the above agents were investigated in a short-term 90%-95% pure ECL cell culture system. Cells were incubated with either the neuromodulator alone or in combination with gastrin for 10-40 minutes, and histamine secretion was measured by enzyme immunoassay. RESULTS: Acetylcholine, isoproterenol, and vasoactive intestinal polypeptide significantly stimulated basal and gastrin-driven histamine secretion, whereas calcitonin gene-related peptide and somatostatin inhibited basal and gastrin-driven histamine secretion. The M1 muscarinic receptor antagonist pirenzepine dose dependently inhibited the action of acetylcholine, whereas the M3 receptor antagonist 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride had no effect. the rest of the evaluated agents had no effect on ECL cell histamine secretion. CONCLUSIONS: These data are consistent with the hypothesis that substantial neurohormonal modulation of ECL cell function exists.

Acetylcholine↗
PubMed1996

The role of transforming growth factor alpha in the enterochromaffin-like cell tumor autonomy in an African rodent mastomys.

BACKGROUND & AIMS: Gastric carcinoids evolved from enterochromaffin-like (ECL) cell hyperplasia are usually associated with high pH and hypergastrinemia. The Mastomys species exhibits a genetic propensity to gastric carcinoid formation that can be accelerated by acid inhibition-induced hypergastrinemia. Although gastrin is critical in the initiation of the ECL cell transformation, the role of other growth factors involved in the evolution of the tumor autonomy has not been established. The aim of this study was to evaluate the role of transforming growth factor (TGF) alpha in the regulation of ECL cell transformation. METHODS: Mastomys were orally administered an irreversible H2-receptor antagonist loxtidine for 0, 8, and 16 weeks, and ECL cell transformation was monitored by assessing gastrin levels, mucosal histamine content, and chromogranin immunoreactivity. The ECL cells were purified, and cell proliferation at each stage in response to gastrin and TGF alpha was measured by bromodeoxyuridine uptake. TGF-alpha expression was evaluated by radioimmunoassay and Northern blot, and epidermal growth factor (EGF) receptor expression was determined by Western blot, immunoprecipitation, and immunocytochemistry. RESULTS: Although the response to gastrin decreased during hypergastrinemia, the proliferative effect of TGF-alpha on ECL cells was specifically amplified during the development of hyperplasia. TGF-alpha and EGF receptor expression increased steadily in the transformed cells. CONCLUSIONS: During low acid-induced hypergastrinemia, the expression of TGF-alpha and EGF receptor may constitute an autocrine regulatory mechanism in ECL cell tumor transformation.

Animals↗
PubMed1996

Evidence for a regulatory role for histamine in gastric enterochromaffin-like cell proliferation induced by hypergastrinemia.

BACKGROUND/AIMS: Hypergastrinemia, induced by sustained suppression of gastric acid secretion, is associated with gastric enterochromaffin-like (ECL) cell hyperplasia and carcinoid tumor formation. We examined the effect of a selective H1-histamine antagonist, terfenadine, on gastric mucosal cell proliferation to determine whether histamine might modulate ECL cell generation. METHODS: The rodent mastomys received the H2-antagonist loxtidine (2 g/l drinking water) alone or in combination with terfenadine (0.5 g/l or 35 mg/l drinking water) for 120 days. Controls received water or terfenadine alone. Serum gastrin levels and tissue histamine content were assayed by radioimmunoassays, and tissue chromogranin levels determined (Western blot analysis). In vivo cell proliferation was measured by bromodeoxyuridine (BrdU, 200 mg/kg/day, 3 days) incorporation. Gastric mucosal thickness was determined, ECL cell number was assessed, and the percentage of proliferating ECL cells quantitated. To evaluate the direct action on ECL cells we then studied the effect of terfenadine on histamine secretion and DNA synthesis (BrdU uptake) in an isolated preparation (approximately 90% pure) of ECL cells. RESULTS: Loxtidine increased serum gastrin levels, mucosal thickness, tissue chromogranin levels, tissue histamine content, BrdU incorporation, ECL cell number, and proliferating ECL cells (all parameters p < 0.05). Terfenadine alone, irrespective of dosage, had no significant effect. The high dose in combination with loxtidine significantly inhibited the increase in tissue chromogranin levels, tissue histamine content, ECL cell number and proliferating ECL cells (p < 0.05), but did not alter other parameters, compared to loxtidine alone. The low does did not alter the loxtidine-induced changes. In pure isolated ECL cells, terfenadine did not alter histamine secretion either alone or in combination with gastrin (10 nM). DNA synthesis was significantly inhibited by terfenadine (IC50 10(-10) M). CONCLUSIONS: Terfenadine specifically inhibited the effect of loxtidine-induced ECL cell proliferation in vivo and significantly inhibited ECL cell DNA synthesis in vitro. We postulate that histamine, through an H1 receptor, positively modulates gastric ECL cell proliferation.

Animals↗
PubMed1996

Somatostatin receptor regulation of gastric carcinoid tumours.

Gastric carcinoids are the sequel of enterochromaffin-like (ECL) cell hyperplasia, and are usually associated with a low-acid state and hypergastrinaemia. The somatostatin (SRIF) analogue octreotide has been noted to decrease both plasma gastrin levels and ECL cell hyperplasia/neoplasia in human and rodent experimental models. The African rodent, mastomys, exhibits a genetic propensity to gastric carcinoid formation which can be significantly accelerated by acid-inhibition-induced hypergastrinaemia. Thus a low-acid state induced by either irreversible H2 blockade or proton pump inhibition shortens the natural 2-year induction time to 4 months. In vivo studies of this model demonstrate that, similar to the human situation, octreotide decreases plasma gastrin levels and inhibits low-acid-induced gastric carcinoid formation. In vitro, using isolated ECL cells, SRIF inhibits both gastrin-stimulated ECL cell histamine secretion and DNA synthesis. This mechanism appears to function via the SRIF receptor (SSTR) subtype 2, which we have identified in both naive and transformed ECL cells. Thus the direct effect of SRIF regulation of ECL cell function is mediated by at least a SSTR2 subtype. It is possible that the alteration of the SSTR2 during ECL cell transformation may contribute to the genetic susceptibility of the mastomys to carcinoid tumour formation. The precise anti-proliferative mechanism of SRIF and its role in neuroendocrine cell transformation remain to be defined. Pharmacological manipulation of the SSTR2 may provide a viable therapeutic and diagnostic target in the management not only of ECL cell neoplasia but also other types of neuroendocrine cell tumour.

Animals↗
PubMed1996

Histidine decarboxylase expression and histamine metabolism in gastric oxyntic mucosa during hypergastrinemia and carcinoid tumor formation.

Histamine is an important stimulator of gastric acid secretion. In experimental animals, inhibition of acid secretion by long term histamine2 receptor blockade causes hypergastrinemia, proliferation of enterochromaffin-like (ECL) cells, and formation of histamine-producing gastric carcinoids. The aim of this study was to examine the role of gastrin in histamine synthesis and metabolism of the oxyntic mucosa of normal, hyperplastic, and carcinoid-bearing Mastomys natalensis. Administration of exogenous gastrin to normal animals increased histidine decarboxylase (HDC) messenger RNA (mRNA) expression in the oxyntic mucosa within 30 min, indicating that gastrin stimulates histamine synthesis by regulating HDC mRNA abundance. Endogenous hypergastrinemia, induced by short term histamine2 receptor blockade (loxtidine) for 3-29 days, did not induce tumors, but enhanced the expression of HDC mRNA (2- to 4-fold elevated) and histamine contents (2-fold elevated) in the oxyntic mucosa. Long term histamine2 receptor blockade (7-21 months) resulted in sustained hypergastrinemia and ECL tumor formation. Tumor-bearing animals had a 4-fold increase in HDC mRNA expression and histamine contents of the oxyntic mucosa. Urinary excretion of the histamine metabolite methyl-imidazole-acetic acid was 2-fold elevated. Tumor-bearing animals recovering from histamine2 receptor blockade were normogastrinemic and had normal levels of HDC mRNA and histamine in the oxyntic mucosa as well as normal excretion of methyl-imidazole-acetic acid. The results indicate that ECL cell carcinoids developing during hypergastrinemia are well differentiated tumors that respond to high gastrin levels with increased histamine synthesis and secretion.

Animals↗
PubMed1996

Pathophysiology of the fundic enterochromaffin-like (ECL) cell and gastric carcinoid tumours.

The genesis of human gastric carcinoma is ill understood but is invariably related to achlorhydria. Gastrin secretion is negatively regulated by luminal acid and hypergastrinaemia is thus associated with low acid states which may be natural (atrophic gastritis) or owing to acid inhibitory therapy. Apart from its acid secretory activity, gastrin is trophic to the mucosa, via stimulation of the fundic enterochromaffin-like (ECL) cells to secrete histamine. In conditions of elevated gastrin levels, ECL cell hyperplasia and even neoplasia have been noted. The relationship between low acid, hypergastrinaemia, ECL cell hyperplasia, and neoplasia may be of relevance since ECL cells secrete histamine and TGF alpha which are both recognised mitogens. We studied the rodent mastomys, which spontaneously develop gastric carcinoid tumours, which can be generated in 4 months under conditions of drug-induced acid inhibition and inhibited by octreotide administration. A pure (90-95%) cell preparation was used to evaluate ECL cell physiology and trophic regulation. A gastrin/CCKB receptor responsible for histamine secretion and DNA synthesis was identified, cloned and sequenced. Octreotide lowers plasma gastrin levels, decreases ECL cell neoplasia and, in vitro, inhibits ECL cell DNA synthesis. H1 receptor antagonists inhibited DNA synthesis in vitro and ECL neoplasia in vivo without altering gastrin levels. Hypergastrinaemia increased TGF alpha/EGF receptor and TGF alpha production and TGF alpha massively stimulated ECL cell DNA synthesis. Since ECL cells produce both histamine and TGF alpha and regulate parietal cells which produce TGF alpha, it is possible that achlorhydria-generated ECL cell dysfunction may play an initiative role in the pathobiology of gastric adenocarcinoma. The long-term clinical consequences of drug-induced sustained acid inhibition are worthy of further consideration.

Animals↗
PubMed1995

Are enterochromaffinlike cell tumours reversible? An experimental study on gastric carcinoids induced in Mastomys by histamine2-receptor blockade.

A rapid induction of enterochromaffinlike (ECL) cell tumours has been shown in Praomys (Mastomys) natalensis subjected to histamine2-receptor blockade. In the present study the reversibility of ECL cell proliferation induced by acid inhibition was investigated. Short-term treatment (8 weeks) with the histamine2-receptor antagonist loxtidine caused a moderate hypergastrinemia, accompanied by a minor increase in histamine contents and a 2-fold increased volume density of the endocrine cells in gastric oxyntic mucosa. Eight weeks after withdrawal of treatment the volume density of endocrine cells was normalised as were the tissue levels of histamine, indicating a total reversibility of ECL cell hyperplasia. Long-term treatment (24 weeks) caused severe changes in the endocrine cell population of the oxyntic mucosa with neoplasia (5/21), dysplasia (11/21) and nodular hyperplasia (5/21). The endocrine cell density increased twofold and tissue histamine levels fourfold. 24 weeks after cessation of treatment, the endocrine cell density had decreased to 136% of controls, while histamine concentrations were normalised. The frequency of invasive carcinoids after recovery (4/23) differed only slightly from that seen after treatment for 24 weeks (5/21). Dysplastic lesions were only seen in 1/23 and hyperplastic lesions were of less severe type after recovery. The results demonstrate that ECL cell hyperplasia and dysplasia, induced by acid inhibition, are reversible after cessation of treatment. However, ECL cell tumours did not disappear, within the given observation period. One may therefore speculate that ECL cell proliferation is no longer reversible once the neoplastic (transformed) phenotype has developed.

Animals↗
PubMed1995

Gastric carcinoids. The Yale Experience.

OBJECTIVES: To document our experience with gastric carcinoids over the past decade and to identify lesion frequency and the existence of a relationship to low acid states. DESIGN: Retrospective case series. SETTING: Tertiary care referral center. PATIENTS: A consecutive sample of 16 patients with gastric carcinoids was evaluated over the last decade. Only two cases were recorded in the prior decade. Ages ranged from 30 to 93 years (mean, 65.9 years). There were eight men and eight women. Three patients were unavailable for follow-up. INTERVENTIONS: Therapy included total gastrectomy (n = 4), subtotal gastrectomy (n = 3), endoscopic polypectomy (n = 3), and endoscopic surveillance (n = 6). MAIN OUTCOME MEASURES: Pathobiological tumor characteristics and survival. RESULTS: All carcinoids were of gastric fundic origin. None of the patients exhibited the carcinoid syndrome. Chronic atrophic gastritis was the most frequently observed comorbid pathologic condition (63%). Half of the patients had multiple polypi. Mean follow-up was 4.7 years (n = 13). There were 10 survivors. The only related death occurred in a patient with a solitary tumor. CONCLUSIONS: Diagnosis of the complex and ill-defined entity of gastric carcinoid is increasing. This may be due to an increased awareness and increased upper gastrointestinal endoscopy rate rather than an increase in real incidence. Criteria for prediction of malignant progression are not available. Multiple gastric carcinoids associated with hypergastrinemia predominantly display nonaggressive behavior. Conservative gastric surgery may be appropriate therapy for such patients.

Adult↗
PubMed1995

Use of an isotopic somatostatin receptor probe to image gut endocrine tumors.

OBJECTIVES: To evaluate the effectiveness of indium In 111 pentetate (diethylenetriaminepentaacetic acid [DTPA]-D-Phe-labeled octreotide scintigraphy in the localization of gastroenteropancreatic neuroendocrine lesions, and to identify covert lesions, determine multicentricity, define the distribution of metastases, confirm complete removal of tumor postoperatively, and evaluate the efficacy of therapeutic embolization. DESIGN: Unmasked comparison. SETTING: Tertiary care referral center. PATIENTS: We studied 28 patients over a 12-month period. Biochemical evidence of a gastroenteropancreatic tumor was present in 13 patients. Octreoscan 111 was employed in four patients with an ambiguous biochemical diagnosis of gastroenteropancreatic tumor. Postoperative examination to document complete tumor removal was undertaken in seven patients. In one patient, Octreoscan 111 was used to evaluate the efficacy of therapeutic embolization. INTERVENTION: [111In]DTPA-D-Phe-octreotide scintigraphy. MAIN OUTCOME MEASURE: Identification of somatostatin receptor-bearing neuroendocrine tumors. RESULTS: Intravenous administration of [111In]DTPA-D-Phe-octreotide followed by whole-body gamma camera scintigraphy resulted in the localization of gastroenteropancreatic neuroendocrine tumors with 75% sensitivity, 100% specificity, 100% positive predictive value, 63% negative predictive value, and 82% overall accuracy. CONCLUSIONS: While Octreoscan 111 has been shown to localize the majority of amine precursor uptake and decarboxylation system (APUD) cell tumors as well as various other somatostatin-positive tumors, this technique may also be useful in a number of other circumstances. These include prediction of tumors that will respond to octreotide therapy, identification of covert metastases, intraoperative identification of tumors, and postoperative surveillance. Use of an alternative isotope may provide a vehicle for the administration of local therapeutic radiation to tumor cells. The precise efficacy of Octreoscan 111 in the identification of lesions smaller than 3 cm with low-density somatostatin-2 receptor expression remains to be determined.

Adult↗
PubMed1995

Adrenergic and cromolyn sodium modulation of ECL cell histamine secretion.

The histamine secreting enterochromaffin-like (ECL) cell is now recognized as the principal regulator of gastric acid secretion. Histamine is not only a primary modulator of acid secretion, but may be of relevance in gastritis and as a mitogen in gastric neoplasia. Study of the ECL cell has been limited since no pure preparation was available. We therefore developed a pure isolated ECL cell preparation with a purity of 90-95% as determined by total histamine content and chromogranin immunofluorescence. Trypan blue exclusion demonstrated > 95% viability. While gastrin and acetylcholine are known modulators of acid secretion, the role of adrenergic neurotransmitters has not been clearly delineated. The purpose of this study was to examine adrenergic modulation of ECL cell histamine release. To further define the inhibitory mechanisms of histamine secretion, we evaluated the mast cell histamine inhibitor sodium cromoglycate. Histamine secretion was determined by radioimmunoassay. Basal secretion was 0.6 +/- 0.2 nmol/10(3) cells. Gastrin stimulated histamine secretion with an EC50 of 3 x 10(-10) M. Octopamine (alpha-adrenergic agonist) (10(-11)-10(-4) M) failed to stimulate histamine secretion. Isoproterenol (beta-adrenergic agonist) stimulated histamine secretion (EC50, 6 x 10(-8) M) and was inhibited by propranolol (IC50 5 x 10(-10) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1995

PYY inhibition of VIP-stimulated ion transport in the rabbit distal ileum.

Vasoactive intestinal polypeptide (VIP) is the pathophysiologic mediator of several small intestinal hypersecretion states. VIP exerts its effect by binding mucosal receptors and ultimately increasing intracellular levels of cAMP. Peptide YY (PYY), a GI hormone concentrated in the distal ileum and colon, has been demonstrated to decrease VIP-mediated secretion in the colon through a specific Y4 mucosal receptor. Characterization of PYY's effect on VIP-stimulated small intestinal secretion may provide a basis for future therapeutic interventions. We hypothesized that ion transport in the small intestine is mediated through a novel Y receptor subtype. We performed Ussing chamber ion transport studies on rabbit ileum using VIP, PYY, and other pancreatic polypeptide (PP)-fold peptides in order to specifically examine: (1) the effects of VIP and PYY on basal and VIP-stimulated short circuit current (Isc), and (2) the changes in VIP-stimulated Isc in response to NPY, PP, leucine31,proline31 neuropeptide Y fragment, ([Leu31,Pro34]NPY) and the carboxy-terminal fragment of NPY (NPY13-36). VIP increased basal Isc in a concentration-dependent manner, while PYY decreased basal Isc. Graded concentrations of PYY decreased VIP-stimulated increases in Isc. PYY added prior to VIP had no effect on VIP-stimulated increases in ISC. Inhibition of VIP-stimulated Isc increases was seen with NPY, but not with [Leu31,Pro34]NPY, PP, or NPY13-36. This distinct pattern of binding affinity characterizes a novel Y receptor subtype. Additionally, increases in Isc by VIP despite pretreatment with PYY suggests that VIP-stimulated ion transport is mediated through mechanisms other than increases in cAMP.

Animals↗
PubMed1995

Octreotide inhibition of serotonin-induced ileal chloride secretion.

Octreotide (SMS, synthetic miniature somatostatin) effectively alleviates the secretory diarrhea of the malignant carcinoid syndrome. Although SMS inhibits tumor release of serotonin (5HT) and other bioactive agents, it also inhibits the diarrhea in patients who continue to exhibit elevated serum levels of 5HT. This observation suggest that SMS may directly inhibit mediator-stimulated intestinal ion secretion at the mucosal level. To test this hypothesis, intestinal ion secretion was studied in rabbit ileal mucosa mounted in Ussing chambers. Maximal changes in short circuit current (delta Isc) were observed as an indicator of mucosal ion secretion. The application of pathophysiologic concentrations of 5HT (10(-5) M) to the mucosal preps resulted in a delta Isc of 52 +/- 6 microA/cm2. This 5HT-stimulated delta Isc was significantly inhibited by serosal furosemide (10(-3) M) or use of a chloride-depleted medium, indicating that 5HT stimulates electrogenic chloride secretion in the rabbit ileum. Pretreatment with a therapeutic concentration of SMS (10(-8) M) resulted in a significant inhibition of 5HT-stimulated electrogenic Cl- secretion (9 +/- 1 microA/cm2) (P < 0.005). This inhibitory effect of SMS was not seen in tissue pretreated with pertussis toxin. The results of these experiments demonstrate that octreotide inhibits 5HT-stimulated electrogenic chloride secretion at the mucosal level. Additionally this inhibitory effect of octreotide is likely mediated by activation of the inhibitory subunit of membrane-bound GTP-binding regulatory proteins. These results thus provide experimental evidence in support of the ability of SMS to ameliorate the carcinoid diarrhea by a direct effect on stimulated mucosal ion secretion.

Animals↗
PubMed1995

Genotoxicity, carcinogenicity and acid-suppressing medications.

With the availability of increasingly potent acid-suppressing medications, questions continue to rise concerning the safety of these compounds in regards to carcinogenetic potential. In this review, we examine current concepts and procedures relating to genotoxicity, the potential for a chemical agent to interact with and alter the genomic information of the cell, and carcinogenesis. A description and discussion of commonly utilized techniques for the determination of (a) in vitro mutagenicity, (b) in vitro and in vivo DNA damage and repair, (c) in vitro and in vivo chromosomal damage and (d) chronically dosed animal tumorigenesis development is presented. Observations from these procedures as they have been applied to a review of the safety of acid-suppressing medications will be discussed. An evaluation of reports relating to potential genotoxic and carcinogenic hazards of therapeutically relevant acid-suppressing medications (cimetidine, ranitidine, omeprazole) is presented. Information related to the effect of prolonged administration of acid-suppressing medications, alterations of serum gastrin levels, and the potential for tumor promotion is discussed.

Animals↗
PubMed1995

A novel serine-specific kinase activity associated with exocrine secretory granules.

Zymogen secretion from exocrine cells involves an exocytotic process that is highly regulated by the modification of cytoplasmic components at different cellular levels. In the present studies, purified secretory granules were prepared from rabbit gastric chief cells, rat pancreatic acinar cells, and parotid glands to characterize a Mg(2+)-dependent protein kinase activity. In chief cell granules, endogenous pepsinogen, a fortuitous substrate, was phosphorylated at optimal Mg2+ and K+ concentrations of 40 and 50 mM, respectively. Adenosine 3',5'-cyclic monophosphate, Ca2+, and calmodulin had no significant effects on the kinase activity. In contrast, Mn2+ or Zn2+ inhibited the kinase activity. In addition to pepsinogen, the exogenous substrates casein, myelin basic protein, and lysine-rich histone were also phosphorylated by the granule-associated kinase. All substrates were exclusively phosphorylated on serine residues. ATP, but not GTP, served as the donor in the phosphorate transfer reaction. Casein kinase (CK) inhibitors CKI-7 and dibromoribofuransylbenzimidazole at concentrations (10 microM) that significantly inhibited CK activities in the tissue homogenate failed to inhibit the granule-associated kinase activity. The kinase activity was localized to the granule membrane and could be removed from the membrane with either 5 mM EDTA or alkaline carbonate extraction. Furthermore, protease digestion sensitivity revealed that the kinase was localized on the cytoplasmic face of the granules. Our results therefore indicate that the secretory granules of exocrine gastric chief cells, pancreatic acini, and parotid acini possess a unique serine-specific protein kinase activity. The cytoplasmic orientation of the kinase activity suggests a possible role in vesicle processing or the exocytotic process.

Amino Acids↗