Biomedical subjects

W R Gower

Publications and source records attributed to W R Gower.

At least 19 recordsLinked to original sources

PubMed1995

Cirrhosis with ascites: increased atrial natriuretic peptide messenger RNA expression in rat ventricle.

BACKGROUND/AIMS: Atrial natriuretic peptides (ANPs) are increased in the circulation of cirrhotics with ascites; however, it is unknown whether this increase is caused by increased synthesis or a decrease in the metabolic processing of these peptides. ANP gene expression in the liver, atria, ventricles, and gastrointestinal tract of cirrhotic vs. control rats was studied as was their metabolism. METHODS: Sprague-Dawley rats developed cirrhosis with ascites approximately 20 weeks after weekly intragastric instillation of carbon tetrachloride. Their circulating, ascitic, and urinary levels of ANPs were measured by radioimmunoassays. ANP gene expression was measured by a ribonuclease protection assay. RESULTS: ANP gene expression was increased 2.8- to 4.1-fold in the ventricles of cirrhotic rats compared with age-matched healthy rats. ANP gene expression was present but not increased in the liver, atria, and gastrointestinal tract of cirrhotic rats. No increase of metabolic processing of these peptides was found in the circulation. Cardiac ultrasonography and catheterization revealed no ventricular dilation or increased ventricular pressure. CONCLUSIONS: Elevation of circulating ANPs with cirrhosis was associated with increased ventricular steady-state ANP messenger RNA concentrations. The increased ANP gene expression in cirrhosis seems to involve a novel mechanism not related to stretch because neither increased ventricular pressure nor dilation was present.

Analysis of Variance↗

PubMed1995

Interleukin-1 receptor antagonist decreases severity of experimental acute pancreatitis.

BACKGROUND: Fulminant acute pancreatitis is a disease of complex origin that results in activation of several of the proinflammatory cytokines. Because interleukin-1 (IL-1) is an integral early component of the acute inflammatory process, the use of an IL-1 receptor antagonist (IL-1ra) was investigated in experimental acute pancreatitis to determine the therapeutic potential of proximal cytokine blockade and to further establish the role of inflammatory cytokines in the pathogenesis of acute pancreatitis. METHODS: IL-1ra was administered in escalating doses either before or after acute edematous, necrotizing pancreatitis was induced in adult male mice by injection of cerulein. The severity of pancreatitis was quantified by serum amylase, lipase, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels, pancreatic wet weight, and blinded histologic grading. RESULTS: Administration of medium (10 mg/kg) and high (100 mg/kg) doses of IL-1ra either before or after the induction of pancreatitis significantly decreased the expected rise in pancreatic wet weight, lipase, IL-6, and TNF-alpha (all, p < 0.01). Serum amylase was significantly reduced when IL-1ra was administered in either dosage before (p < 0.05), but not after, induction of pancreatitis. Pancreatic edema, necrosis, and inflammatory cell infiltrate were significantly diminished (p < 0.05) by histologic grading in all animals receiving medium or high doses of IL-1ra. Low doses of IL-1ra (1.0 mg/kg) had modest effects if given before, but no effect if given after, induction of pancreatitis. CONCLUSIONS: The proinflammatory cytokines IL-6 and TNF-alpha are elevated during experimental acute pancreatitis and correlate well with the severity of local pancreatic destruction. Blockade of the cytokine cascade at the level of the IL-1 receptor before or soon after induction of pancreatitis significantly attenuates the rise in these cytokines and is associated with decreased severity of pancreatitis and reduced intrinsic pancreatic damage.

Acute Disease↗

PubMed1995

Decreased mortality of severe acute pancreatitis after proximal cytokine blockade.

OBJECTIVE: This study determined the ability of interleukin-1 receptor antagonist (IL-1ra) to decrease the mortality of experimental acute pancreatitis. The response of the inflammatory cytokine cascade and its subsequent effects on pancreatic morphology were measured to determine the role of these peptides in mediating pancreatic injury. SUMMARY BACKGROUND DATA: Previous studies have shown that proinflammatory cytokines are produced in large amounts during acute pancreatitis and that blockade at the level of the IL-1 receptor significantly decreases intrinsic pancreatic damage. The subsequent effect on survival is not known. METHODS: A lethal form of acute hemorrhagic necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented (CDE) diet for 72 hours. For determination of mortality, the animals were divided into 3 groups of 45 animals each: control subjects received 100/microL normal saline intraperitoneally every 6 hours for 5 days; IL-1ra early mice received recombinant interleukin-1 receptor antagonist 15 mg/kg intraperitoneally every 6 hours for 5 days beginning at time 0; IL-1ra late mice received IL-1ra 15 mg/kg intraperitoneally every 6 hours for 3.5 days beginning 1.5 days after introduction of the CDE diet. A parallel experiment was conducted simultaneously with a minimum of 29 animals per group, which were sacrificed daily for comparisons of serum amylase, lipase, IL-1, IL-6, tumor necrosis factor-alpha, IL-1ra, pancreatic wet weight, and blind histopathologic grading. RESULTS: The 10-day mortality in the untreated control group was 73%. Early and late IL-1ra administration resulted in decreases of mortality to 44% and 51%, respectively (both p < 0.001). Interleukin-1 antagonism also was associated with a significant attenuation in the rise in pancreatic wet weight and serum amylase and lipase in both early and late IL-1ra groups (all p < 0.05). All control animals developed a rapid elevation of the inflammatory cytokines, with maximal levels reached on day 3. The IL-1ra-treated animals, however, demonstrated a blunted rise of these mediators (all p < 0.05). Blind histologic grading revealed an overall decrease in the severity of pancreatitis in those animals receiving the antagonist. CONCLUSIONS: Early or late blockade of the cytokine cascade at the level of the IL-1 receptor significantly decreases the mortality of severe acute pancreatitis. The mechanism by which this is accomplished appears to include attenuation of systemic inflammatory cytokines and decreased pancreatic destruction.

Acute Disease↗

PubMed1995

Secretion and renal effects of ANF prohormone peptides.

1. Atrial natriuretic factor (ANF) and pro ANF peptide appears to be secreted simultaneously from the atria in response to atrial stretch. 2. The major peptide forms secreted from rat atria appear to be ANF (pro ANF 99-126) as the primary C-terminal peptide and pro ANF 1-30 as the primary N-terminal peptide, as opposed to 1-67 or 1-98. 3. The plasma concentrations of ANF and pro ANF 1-30 are increased by acute stimulation with blood volume expansion and the plasma levels of ANF and N-terminal ANF prohormone peptides are chronically elevated by high salt diet. 4. Pro ANF 31-67 produces a natriuresis which is not dependent on an increase in renal cGMP excretion, decreases in plasma renin activity (PRA) or elevations in plasma ANF concentration.

Animals↗

PubMed1995

Release of kaliuretic peptide during immersion-induced central hypervolemia in healthy humans.

Kaliuretic peptide, a new peptide hormone consisting of amino acids 79-98 of the 126 amino acid atrial natriuretic factor (ANF) prohormone, is synthesized in the heart and is a potent stimulator of potassium excretion. The mechanism(s) controlling the release of kaliuretic peptide heretofore has not been defined. Because water immersion to the neck provides an acute central volume expansion identical to that produced by 2 liters of saline but without the plasma compositional change, immersion to the neck (NI) was utilized to assess kaliuretic peptide responses to acute central blood volume expansion in seven seated sodium-replete normal subjects. Since atrial natriuretic factor (ANF; amino acids 99-126 of the prohormone) originates from the amino acids adjacent to kaliuretic peptide in the ANF prohormone but is proteolytically cleaved from the rest of the prohormone before release, measurement of ANF was incorporated into this study to determine if there are differences with respect to release of these two portions of the ANF prohormone. Both kaliuretic peptide and ANF increased promptly with NI, with ANF peaking at 1 hr of immersion, whereas kaliuretic peptide peaked at the 3rd hr of immersion. With cessation of immersion, ANF decreased to preimmersion levels within 0.5 hr while kaliuretic peptide was still significantly (P < 0.05) elevated at 1 hr postimmersion. These findings indicate that kaliuretic peptide and ANF are released simultaneously but that kaliuretic peptide peak circulating concentration and its return to preimmersion values are prolonged compared with ANF. These last findings suggest a slower clearance from the circulation for kaliuretic peptide. The diuretic peak response to NI corresponded in a temporal manner to the peak circulating concentration of kaliuretic peptide, suggesting a possible physiologic role for kaliuretic peptide in modulating volume homeostasis in humans.

Adult↗

PubMed1994

Tumor necrosis factor-alpha induces the expression of carbonic anhydrase II in pancreatic adenocarcinoma cells.

TNF is a 17kD cytokine classically known for its cytotoxic effects on malignant cells. More recent cell culture studies demonstrated TNF induced cytostasis associated with the expression of a terminally differentiated phenotype. This was best characterized in malignant hematopoietic models, although a similar action on cells derived from solid tumors is now increasingly recognized. In the present study, six day exposure to TNF (40 ng/ml) stimulated morphologic changes in a human pancreatic adenocarcinoma cell line (HPAC), including increased cellular homogeneity, decreased nuclear to cytoplasmic ratio and detachment from the cell monolayer. Proliferation and DNA synthesis were reversibly inhibited while cellular viability was maintained. Parallel to the changes in morphology and growth was the delayed appearance of carbonic anhydrase II (CA II, E.C. 4.2.1.1), an accepted marker for pancreatic cells of ductal origin. A concomitant increase in the steady-state level of CA II mRNA was also observed over the time-course of TNF exposure. These results suggest a novel role for TNF in the induction of a more terminally differentiated ductal cell phenotype in a human pancreatic carcinoma model.

Adenocarcinoma↗

PubMed1994

Functional glucocorticoid receptor modulates pancreatic carcinoma growth through an autocrine loop.

Several peptide hormones have been shown to influence growth and function in pancreatic carcinoma and have given evidence for an autocrine feedback loop governing the proliferation of these malignant cells. Conversely, steroid hormones including glucocorticoids have been shown to inhibit the growth of pancreatic cancer cells; however, the prevalence of the glucocorticoid receptor or its mechanism of growth suppression in these tumors is unknown. The ability of growth factors thought to be active in this autocrine loop to reverse the glucocorticoid-induced growth inhibition was studied in vitro in a human pancreatic adenocarcinoma (HPAC) cell line with a well-characterized glucocorticoid receptor (GR). The glucocorticoid dexamethasone (DEX) inhibited growth in a dose-dependent manner as measured by a [3H]thymidine incorporation assay as well as an MTT cell proliferation assay. Maximal effects were seen within 48 hr at a concentration of 100 nM DEX, suppressing growth to approximately 18% of control. When the maximally suppressed DEX-treated cells were exposed to exogenous growth factors, they rapidly attained or exceeded the growth rate of control cells: insulin-like growth factor = 106%, transforming growth factor-alpha = 134%, insulin = 151%, and epidermal growth factor = 187% (all P < 0.05, Student's t test). In order to determine the frequency of the GR in pancreatic cancer and the clinical relevance of our findings, immunohistochemical staining for the GR was performed on 20 human tumors. Twelve (60%) of all cancers, as well as all normal pancreatic tissues (n = 4), stained positively for cytoplasmic and/or nuclear GR with expression correlating highly with degree of tumor differentiation (Kruskal-Wallis test, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma↗

PubMed1992

Hepatic function after porto-systemic shunt.

Advanced hepatic injury can be identified by the appearance of jaundice, coagulopathy, or encephalopathy but these conditions are late, irreversible findings and represent the end stage of a long insidious process. Currently available methods for assessing "liver function" (SGOT, SGPT, GGT, LDH, etc.) do not actually measure liver function. In this study we prospectively evaluated "true" liver function in patients undergoing porto-systemic shunt. Effective hepatic blood flow [low dose galactose clearance (EHBF)], hepatocyte transport (theophylline levels at 24 hr), and hepatic conjugation ability [acetaminophen metabolism to its glucuronide and sulfate conjugates ( (S + G)/A) and acetaminophen remaining at 24 hr (A24)] were measured in normal males (NL) and in patients pre- and post-8-mm H-graft portacaval shunt (PCS). All data are means +/- SEM, analyzed by Student's t test, and significance was accepted if P less than 0.05. There were no significant differences in EHBF even after PCS. Hepatocyte transport was decreased in pre-op (1.43 +/- 0.16 vs 0.74 +/- 0.08) and post-op (1.79 +/- 0.34) PCS patients. Hepatic conjugating ability was also decreased in pre-op PCS patients [A24 was increased (0.24 +/- 0.11 vs 0.01 +/- 0.01) while the ratio of conjugation products to acetaminophen remained the same]. The ability of the liver to conjugate substrate was severely compromised postoperatively [A24 - 1.27 +/- 0.67, (S + G)/A - 1.19 +/- 0.34]. We believe that changes in liver function can be accurately measured using these noninvasive methods, and in using these methods we have identified altered hepatocyte transport and conjugating ability in patients undergoing porto-systemic shunt surgery.

Acetaminophen↗

PubMed1991

Atrial natriuretic factor: a possible new gastrointestinal regulatory peptide.

Although associated primarily with the cardiovascular system, atrial natriuretic factor (ANF) has been found to increase the magnitude of duodenal contractions and may play a role in salt and water absorption across gastrointestinal epithelium. Because secretory diarrhea and increased peristalsis are commonly associated with conditions related to hypergastrinemia, we examined an animal model of hypergastrinemia (fundusectomy) to evaluate a possible role for ANF. Sprague-Dawley rats underwent either fundusectomy or sham operation. Circulating levels of gastrin (1085 +/- 105 vs 59 +/- 5 pg/ml), ANF (209 +/- 50 vs 59 +/- 10 pg/ml), and pro-ANF 1-98 (786 +/- 80 vs 599 +/- 49 pg/ml) were elevated significantly 3 months after fundusectomy versus control animals. The increased levels of ANF and pro-ANF 1-98 correlated with the increased gastrin levels (p less than 0.05). Tissue content of ANF and pro-ANF 1-98 were determined at sequential sites in the stomach and small intestine. In normal rats ANF concentrations were greatest in the small intestine; pro-ANF 1-98 content was similar in all tissues except ileum (increased). In rats that underwent fundusectomy, ANF and pro-ANF 1-98 were markedly increased in duodenum compared with all other tissues. Only duodenum showed a difference in peptide levels between normal rats and rats that underwent fundusectomy, (ANF, 1.5 +/- 0.5 vs 16.7 +/- 2.3 ng/gm; pro-ANF 1-98, 0.6 +/- 0.3 vs 51.2 +/- 36.1 ng/gm). Circulating ANF and pro-ANF 1-98 are increased in rats that have undergone fundusectomy. Our results suggest that duodenum may be the source of these increased levels.

Animals↗

PubMed1990

Endocrine neoplasms (non-gastrin) of the pancreas.

Although neoplasms that produce gut regulatory peptides and amines can be found throughout the gastroenteropancreatic axis (excluding carcinoids), the vast majority of these lesions are found within the pancreas. Recognition of the various clinical syndromes produced by the secretions of these tumors, the development of sensitive and specific radioimmunoassays for the elaborated peptides, and development of more effective localization techniques have contributed to earlier diagnosis and marked improvement in patient care. Treatment is directed toward medical management to correct the metabolic disturbances produced by the excessive amounts of gut regulatory peptides, followed by localization and extirpation of tumor. In the presence of unresectable tumor or metastases, palliative treatment directed at reducing peptide secretion or preventing its effects by surgery, chemotherapy, hormonal therapy, and hepatic-artery embolization can produce long-term remission of symptoms. Because the majority of these tumors are malignant, the ultimate goal in successful patient management is the early detection and surgical excision of the islet cell tumor before metastases occur.

Adenoma, Islet Cell↗

PubMed1990

Gastrinoma in vitro: morphological and physiological studies of primary cell cultures.

Functional gastrin-containing tumor cells were maintained for up to 8 wk without fibroblastoid cell overgrowth. Short-term cultures consisted mainly of colonies composed of small polygonal cells, 70%-90% of which stained positive for immunoreactive gastrin. Cultures exhibited limited growth but viability remained high for 2-3 wk. Culture medium contained component I, and gastrin 34, 17, and 14. With time the major C-terminal gastrin species in medium changed from gastrin 17 at 3 days to gastrin 34 at 5 wk. Extracts of cultured cells contained gastrin 34, 17, and 14; gastrin 17 was the major form detected at all times. Ultrastructurally, cultured tumor cells retained morphological integrity for several weeks; however, with time changes in the appearance of the secretory granules accompanied by evidence of cellular retrodifferentiation were gradually observed. Secretin, gastrin-releasing peptide, 8-bromoadenosine 3':5'-cyclic monophosphate, and phorbol, 12-myristate, 13-acetate stimulated the release of gastrin from cultured cells in a time-dependent fashion. Secretin, bombesin, gastrin-releasing peptide, L-tryptophan, and ethylamine stimulated gastrin release in a dose-dependent fashion. Somatostatin 14 inhibited secretin, bombesin, and gastrin-releasing peptide stimulated gastrin release but did not alter basal release. Cultured cells demonstrated de novo gastrin synthesis, evidenced by their ability to incorporate radiolabeled amino acids into immunoadsorbable gastrinlike material. Primary cultures of gastrin-containing tumor cells free from stromal contamination offer unique advantages for studies of factors that regulate the synthesis and secretion of gastrin and may prove of potential value for studies on cell differentiation and growth.

Culture Media↗

PubMed1990

Posttranslational gastrin processing depends on tumor morphology.

Extracellular matrices have recently been demonstrated to alter cell morphology in culture. Altered cell morphology has been associated with changes in gene transcription and translation, but it is not known whether it also affects posttranslational processing. Using tyrosine-O-sulfation as a marker of processing, we studied the effects of various substrates on biologically active gastrin (IRG) production and sulfation in gastrin-containing tumor cells (GT cells). Dispersed GT cells were plated onto different substrates and then incubated. Culture media from days 4, 7, and 28 were assayed with specific antibodies that recognize total IRG and nonsulfated IRG. Cells cultured on plastic and dried films of laminin, collagen, and Matrigel (Collaborative Research Inc., Lexington, Mass.) flattened and formed monolayers of GT cells. Cells cultured on a porous membrane and hydrated gels of collagen and Matrigel did not flatten but formed spheroids of GT cells. The monolayer cultures showed an increase in sulfation with time but a decrease in IRG production. The spheroid cultures maintained a constant level of sulfation over time and, with the exception of Matrigel (gel), also showed a decrease in IRG production. These results indicate that the level of sulfation was unchanged from that of the original tumor when cells were grown in spheroids but increased when cultured as monolayers. It appears that alteration of the cellular milieu alters colony morphology, which in turn alters gastrin processing.

Cell Survival↗

PubMed1989

Is there a fundic factor which regulates G cells in the antrum?

Both surgical fundusectomy and pharmacologic acid inhibition have been shown to produce antral G cell hyperplasia in rats. Fundusectomy has also been shown to be a reliable, reproducible means to produce hypergastrinemia. In contrast, treatment of animals with famotidine, a histamine H2 receptor antagonist, or omeprazole, a H+-K+-ATPase enzyme inhibitor, failed to produce hypergastrinemia. This suggests that elimination of acid inhibition may not be the sole mechanism of hypergastrinemia after fundusectomy. We hypothesized that removal of the gastric fundus may remove a factor which controls G cell activity.

Animals↗

PubMed1989

Fundusectomy-induced hypergastrinemia is not due to acid inhibition alone.

Hypergastrinemia is often attributed to loss of acid inhibition in the gastric antrum. Prior studies suggest, however, that hypergastrinemia after fundusectomy occurs earlier and to a greater degree than hypergastrinemia after total acid inhibition with high dose (8 mg/kg/day) famotidine. To explain the very early (0 to 21-day) gastrin response, 45 male Sprague-Dawley rats (250 to 350 gm) were equally allocated to fundusectomy alone, famotidine alone, and fundusectomy plus famotidine groups. Vena cava blood samples and antral tissue were harvested at 0, 4, 7, 9, 14, and 21 days. Fundusectomy produced dramatic, sustained hypergastrinemia as early as 4 days after the procedure. Minimal, transient hypergastrinemia was seen with famotidine treatment, but this returned to baseline in spite of total acid inhibition. Antral gastrin was comparable in all three groups at the intervals assessed. Furthermore, fundusectomy plus famotidine did not demonstrate a significant difference from fundusectomy alone. Thus it appears that fundusectomy produces early and sustained hypergastrinemia by a mechanism other than acid inhibition.

Animals↗

PubMed1988

Control of gastrin release in cultured gastrinoma-derived G cells.

Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1987

Effect of somatostatin analogue (SMS 201-995) on molecular species of gastrin in gastrinoma.

Somatostatin analogue (SMS 201-995) has been shown to decrease total serum gastrin in patients with gastrinoma; however, the gastrin level rarely returns to normal, despite the near-complete inhibition of acid secretion. This implies that SMS may have an inhibitory action on the biologically active molecular species of gastrin and have little effect on biologically inactive species. To test this hypothesis, we determined the effect of SMS on the molecular species of gastrin in eight patients with the Zollinger-Ellison syndrome. Serum obtained before treatment and 6 hours and 18 hours after treatment (SMS 1 microgram/kg, subcutaneously) was sampled and assayed for molecular species of gastrin by means of gel filtration chromatography and fractional quantitation of gastrin species by radioimmunoassay. There was a significant decrease in the amount of G-34 and G-17 species. BBG and G-14 decreased, a change not significant at 6 hours but significant 18 hours after SMS. The distribution of the various molecular species as a percent of total immunoreactive gastrin was analyzed before and after SMS. There was a shift in the distribution of the molecular species, so that 6 hours after SMS treatment nearly 50% of total gastrin activity was accounted for by BBG and component I. SMS seems to have a different potency to inhibit release of the various gastrin molecular species. This observation may explain the failure of total gastrin levels to return to normal after SMS treatment in patients with the Zollinger-Ellison syndrome.

Aged↗

PubMed1986

Characterization of the in vivo and in vitro inhibition of gastrin secretion from gastrinoma by a somatostatin analogue (SMS 201-995).

Earlier experiments characterized the effect of SMS 201-995 on gastrin secretion from gastrinoma in vivo. The results showed that the somatostatin analogue inhibits basal as well as secretin- and calcium-stimulated gastrin secretion. The current study examined the effect of SMS 201-995 on gastrin secretion from gastrinoma in vitro. Gastrinoma cells were prepared in cell culture or acute cell dispersion to study basal gastrin release. In cell culture, SMS 201-995 at 10(-9) M, 10(-8) M, and 10(-7) M significantly stimulated gastrin secretion (basal medium gastrin, 157 +/- 7.9 pg/ml; with SMS 201-995 10(-9) M, 786 +/- 62 pg/ml; with SMS 201-995 10(-8) M, 569 +/- 72 pg/ml; and with SMS 201-995 10(-7) M, 258 +/- 26 pg/ml). In contrast, in acute cell dispersion, the somatostatin analogue inhibited gastrin secretion (basal medium gastrin, 12.8 +/- 1.3 ng/ml; with SMS 201-995 10(-9) M, 9.0 +/- 0.1 ng/ml; with SMS 201-995 10(-8) M, 8.4 +/- 1.5 ng/ml; and with SMS 201-995 10(-7) M, 7.9 +/- 0.2 ng/ml). Gastrinoma cells were prepared in cell culture to study the effect of SMS 201-995 on gastrin secretion stimulated by secretin and by post-receptor increases in adenosine cyclic nucleotide. The somatostatin analogue inhibited gastrin secretion stimulated by secretin (10(-6) M) (797 +/- 48 pg/ml for secretin alone, compared with 396 +/- 9.4 pg/ml for secretin plus SMS 201-995). SMS 201-995 did not inhibit gastrin secretion stimulated by dibutyryl cyclic AMP (10(-7) M) (617 +/- 62 pg/ml for dibutyryl cyclic AMP alone, compared with 778 +/- 55 pg/ml for the two together). In vitro, SMS 201-995 inhibits basal gastrin secretion from gastrinoma prepared in acute cell dispersion, but not gastrinoma in cell culture, probably due to differences in basal secretory rates. The effect in vitro is less than that in vivo. SMS 201-995 does not inhibit postreceptor increases in adenosine nucleotide. This indirectly supports the hypothesis that SMS 201-995 acts in gastrinoma cells to inhibit gastrin secretion by inhibition of adenylate cyclase activity.

Adult↗

PubMed1986

Hyperparathyroid glands contain G-17 and G-34 gastrin.

To determine if gastrin in hyperparathyroid glands is true gastrin or artifact and to determine the frequency of gastrin in parathyroid glands, 20 parathyroid glands from 11 patients with hyperparathyroidism but without MEA were extracted and analyzed for gastrin. The parathyroid glands from 4 out of 11 patients had measurable gastrin immunoreactivity (10.7 + 6 pg/mg tissue). Column separation chromatography confirmed that this was true gastrin (40% G-34; 50% G-17). Immunohistochemistry with ABC (avidin biotin complex) immunoperoxidase confirmed the presence of gastrin in cytoplasmic vesicles in scattered parathyroid cells. True gastrin does exist in some cells in some patients with hyperparathyroidism.

APUD Cells↗