Pancreastatin-like Immunoreactivity Research Articles

Chromogranin A and pancreastatin-like immunoreactivity in normal pregnancies.

Placenta is a neuroendocrine organ, and we therefore wanted to study the occurrence of the general neuroendocrine marker chromogranin A (CgA) and its split product pancreastatin. CgA and pancreastatin-like immunoreactivity (PST-LI) were determined by ELISA and RIA methods, respectively, in homogenates from term placentas, sera from pregnant women, nonpregnant women, umbilical cords, and in amniotic fluids. In placental homogenates, the mean level of CgA was 7.1 +/- 8.6 pmol/g wet wt (mean +/- SD), whereas PST-LI was not detectable. CgA immunoreactivity was demonstrated by immunofluorescence studies of isolated trophoblasts and decidual cells from term placentas. In trophoblasts, CgA was colocalized with human chorionic gonadotropin (hCG) and human placental lactogen. By Northern blotting, a distinct band corresponding to CgA messenger RNA (mRNA) was demonstrated in the placental cell line, whereas, in placental homogenates, a mRNA band of a slightly larger size was found. Median CgA level in maternal sera at term tended to be higher (median: 469 pmol/L, range 61-980 pmol/L, P < 0.1) than at 6-11 weeks (286 pmol/L, 61-653 pmol/L) or in sera from nonpregnant women (306 pmol/L, 204-469 pmol/L). In umbilical cord sera, median CgA level was significantly higher (898 pmol/L, 102-2245 pmol/L, P < 0.05) than in term sera. Median serum level of PST-LI was significantly higher at term (38 pmol/L, 0-131 pmol/L) than at 6-11 weeks (9 pmol/L (0-85 pmol/L, P < 0.05), than in nonpregnant women (6 pmol/L, 0-52 pmol/L, P < 0.05), and in umbilical cord sera (12 pmol/L, 0-76 pmol/L, P < 0.05). In amniotic fluid, median CgA value was significantly higher at term (1163 pmol/L, 714-1673 pmol/L) than at 14-17 weeks (551 pmol/L, 82-980 pmol/L, P < 0.01), whereas median level of PST-LI was significantly higher at 14-17 weeks (32 pmol/L, 6-97 pmol/L) than at term (0 pmol/L, 0-15 pmol/L, P < 0.01). To our knowledge, this is the first report describing the presence of CgA and PST-LI in placenta and amniotic fluid and the occurrence CgA mRNA in placental tissue and in a placental cell line. The presence of CgA in placenta may indicate a physiological role in pregnancy.

Chromogranin A and pancreastatin-like immunoreactivity in normal pregnancies

Chromogranin A and pancreastatin-like immunoreactivity in normal pregnancies

Gastrin-evoked secretion of pancreastatin and histamine from ECL cells and of acid from parietal cells in isolated, vascularly perfused rat stomach. Effects of isobutyl methylxanthin and α-fluoromethylhistidine

The ECL cells in the rat stomach release pancreastatin and histamine in response to gastrin stimulation. The present study compares the release of pancreastatin and histamine from the ECL cells and the secretion of acid from the parietal cells in response to gastrin, and examines how a markedly reduced histamine content in the ECL cells will affect the gastrin-evoked release of pancreastatin and the secretion of gastric acid. Totally isolated, vascularly perfused stomachs were prepared from fasted rats. Some of the rats had been pre-treated for 24 h with (α-fluoromethylhistidine (α-FMH), resulting in 80% depletion of oxyntic mucosal histamine (mainly ECL-cell histamine). The stomachs were perfused with rat gastrin-17, α-FMH, isobutyl methylxanthine (IBMX), or vehicle in various combinations for 8 h. The venous outflow was collected (30-min samples) for determination of histamine and pancreastatin-like immunoreactivity (LI) and the gastric luminal outflow was collected for determination of H +. Gastrin raised the outflow of pancreastatin-LI and histamine but did not raise the acid output unless IBMX was added. The outflow of pancreastatin-LI and histamine was greater after gastrin + IBMX (at least during the first 4-h period) than after gastrin alone. α-FMH reduced gastrin-evoked histamine outflow but did not affect gastrin-evoked pancreastatin-LI outflow. Also the acid output in response to gastrin + IBMX was much reduced by α-FMH. In conclusion, increased levels of intracellular cAMP enhanced the gastrin-evoked release of pancreastatin-LI and histamine from the ECL cells and made it possible for histamine, released from the ECL cells, to cause acid secretion from the parietal cells. ECL-cell histamine depletion reduced the gastrin-evoked acid secretion; it did not affect the gastrin-evoked release of pancreastatin-LI.

Gastrin-evoked secretion of pancreastatin and histamine from ECL cells and of acid from parietal cells in isolated, vascularly perfused rat stomach. Effects of isobutyl methylxanthin and α-fluoromethylhistidine

The ECL cells in the rat stomach release pancreastatin and histamine in response to gastrin stimulation. The present study compares the release of pancreastatin and histamine from the ECL cells and the secretion of acid from the parietal cells in response to gastrin, and examines how a markedly reduced histamine content in the ECL cells will affect the gastrin-evoked release of pancreastatin and the secretion of gastric acid. Totally isolated, vascularly perfused stomachs were prepared from fasted rats. Some of the rats had been pre-treated for 24 h with (α-fluoromethylhistidine (α-FMH), resulting in 80% depletion of oxyntic mucosal histamine (mainly ECL-cell histamine). The stomachs were perfused with rat gastrin-17, α-FMH, isobutyl methylxanthine (IBMX), or vehicle in various combinations for 8 h. The venous outflow was collected (30-min samples) for determination of histamine and pancreastatin-like immunoreactivity (LI) and the gastric luminal outflow was collected for determination of H+. Gastrin raised the outflow of pancreastatin-LI and histamine but did not raise the acid output unless IBMX was added. The outflow of pancreastatin-LI and histamine was greater after gastrin + IBMX (at least during the first 4-h period) than after gastrin alone. α-FMH reduced gastrin-evoked histamine outflow but did not affect gastrin-evoked pancreastatin-LI outflow. Also the acid output in response to gastrin + IBMX was much reduced by α-FMH. In conclusion, increased levels of intracellular cAMP enhanced the gastrin-evoked release of pancreastatin-LI and histamine from the ECL cells and made it possible for histamine, released from the ECL cells, to cause acid secretion from the parietal cells. ECL-cell histamine depletion reduced the gastrin-evoked acid secretion; it did not affect the gastrin-evoked release of pancreastatin-LI.

Pancreastatin-like immunoreactivity in globular dystrophic neurites of senile plaques in brains of patients with Alzheimer's disease

The immunohistochetnical localization of pancreastatin (PST) was examined in brains of Alzheimer's disease (AD) and control cases using three different antisera to PST, and was compared with the staining for chromogranin A (CgA), the precursor of PST. In control brains, CgA-like immunoreactivity was observed in the cytoplasm and fibers of certain neuronal populations, which were not immunostained with any of the PST antisera. In AD brains, dystrophic neurites of globular shape located in senile plaques were immunostained with each of the PST antisera, as well as with the CgA antibody. PST positive and CgA-positive dystrophic neurites showed similar profiles. The present study indicates that CgA is probably cleaved to produce PST in some globular dystrophic neurites in senile plaques.

Plasma pancreastatin-like immunoreactivity correlates with plasma norepinephrine levels in essential hypertension

Pancreastatin (PST), a 49 amino acid peptide originally isolated from porcine pancreas, is derived from chromogranin A (Cg A), an acidic protein co-released with catecholamines from sympathetic nerve terminals and chromaffin cells. Extracellular processing of Cg A yields PST as well as other biological active peptides. Measurement of Cg A and PST-like immunoreactivity (PST-LI) has been used to investigate patients with pheochromocytoma and other neuroendocrine neoplasia. Some studies have found increased plasma norepinephrine (NE) levels in essential hypertension. We therefore measured venous plasma PST-L1 and catecholamines in patients with essential hypertension. We employed a radioimmunoassay developed with commercially available reagents for measuring plasma PST-like immunoreactivity, and HPLC with electrochemical detection for measurement of plasma catecholamines. The correlation of PST-LI with epinephrine (E) was very weak. However, its correlation with NE was highly significant. Thus, venous plasma PST-LI immunoreactivity may reflect sympathetic nerve activity in essential hypertension.

Circulating pancreastatin is a marker for the enterochromaffin-like cells of the rat stomach

Background/Aims Peptides of the chromogranin family occur in peptide hormone—producing cells throughout the body. One source of such peptides is the enterochromaffin-like (ECL) cells, which constitute the predominant population of endocrine cells in the fundus (the acid-producing part) of the rat stomach. The purpose of this study was to examine whether ECL cells, which are controlled by gastrin, represent a major source of circulating pancreastatin, a fragment of chromogranin A. Methods Rats underwent surgical procedures and treatments in which the ECL cells could be manipulated. The procedures included antrectomy, fundectomy, and gastrectomy (and adrenalectomy), and the treatments included fasting or feeding, gastrin-17 infusion, and administration of omeprazole or ranitidine. The concentrations of pancreastatin-like immunoreactivity (LI) and gastrin in the serum were determined by radioimmunoassay. Results The serum pancreastatin-LI concentration was lowered by about 80% by fundectomy and gastrectomy; both of these procedures eliminated the ECL cell population. Adrenalectomy had no effect on the serum pancreastatin-LI concentration. Gastrin infusion, which activates the ECL cells, promptly increased serum pancreastatin-LI concentration. Refeeding after fasting and administration of omeprazole or ranitidine increased the serum pancreastatin-LI concentrations; these responses were prevented by antrectomy. Conclusions The concentration of circulating pancreastatin-LI reflects the activity of the ECL cells and the size of the ECL cell population in the rat stomach.

Increased plasma pancreastatin-like immunoreactivity levels in non-obese patients with essential hypertension

Pancreastatin, a novel peptide, is known to inhibit insulin secretion and to have a glycogenolytic effect, and is present in many endocrine and chromaffin cells. Both the plasma insulin levels and the adrenergic activity accompanying insulin resistance have been shown to be increased in hypertensive subjects. Our working hypothesis was that pancreastatin might play a role in these pathological phenomena. We studied the plasma pancreastatin level in non-obese essential hypertensive patients in response to an intravenous glucose load. We further measured the responses to the glucose challenge of insulin, glucagon, catecholamines and free fatty acids, as well as other factors related to insulin resistance (i.e. lipoproteins and apolipoproteins). We separated the hypertensive patients into three groups according to their response to an oral glucose-tolerance test: normoinsulinaemic, hyperinsulinaemic and glucose-intolerant. Matched normotensive control subjects were also studied. Pancreastatin levels did not change in the control group after the glucose challenge. However, all hypertensive patients showed an increase in plasma pancreastatin levels after glucose loading. The normoinsulinaemic hypertensive patients also had elevated basal pancreastatin levels. The increase in pancreastatin levels was in the ranking: normoinsulinaemic > hyperinsulinaemic > glucose-intolerant. The pancreastatin: insulin ratio showed that the secretion of pancreastatin and insulin may be regulated differently. Basal free fatty acid and glucagon levels were found to be elevated both in the hyperinsulinaemic and in the glucose-intolerant group. Fasting triglycerides levels were increased in all of the hypertensive patients. Other risk factors for coronary artery disease were also found to be altered: elevated very low-density lipoprotein-cholesterol and decreased high-density lipoprotein-cholesterol, with ranking: normoinsulinaemic < hyperinsulinaemic < glucose-intolerant. These results show an increase in pancreastatin levels in hypertensive patients, suggesting that pancreastatin might play a role in the pathophysiology of essential hypertension.

Pancreastatin-like immunoreactivity of cerebrospinal fluid in patients with Alzheimer type dementia: evidence of aberrant processing of pancreastatin in Alzheimer type dementia

The concentrations of pancreastatin-like immunoreactivity (PST-LI) of the cerebrospinal fluid (CSF) were measured in the patients with Alzheimer type dementia (ATD) and in age-matched normal subjects. The mean PST-LI concentration in the CSF of ATD patients was significantly lower than that of normal subjects. Gel chromatographic analysis revealed that the main PST-LI peak of ATD's CSF eluted at molecular weight (MW) 13.5 kDa. However, the age-related change of the molecular forms of PST-LI in CSF was observed in normal subjects as following; PST-LI in neonatal CSF showed one peak at MW 13.5 kDa, that of 16–64-year-old showed two peaks at MW 13.5 and 5.4 kDa, however, only one main peak was shown at MW 5.4 kDa in the CSFs of 72–85-year-old. These findings suggest that the production of PST-LI was decreased and the proteolytic cleavage, which should process big PST to PST (1–52) in normal subjects, was altered to that of neonatal type in the CNS of the patients with ATD.

Immunoassays for measurement of chromogranin a and pancreastatin-like immunoreactivity in humans: Correspondence in patients with neuroendocrine neoplasia

Chromogranin A (CgA) is a useful marker of neuroendocrine tumors in humans. Here we describe and compare two immunoassay methods for determination of CgA, a radioimmunoassay (RIA) and an enzyme linked immunoassay (ELISA). The detection limit of the ELISA was lower than that of the RIA method (2 ng/ml versus 10 ng/ml, respectively), though the CgA RIA method covered a wider range than the CgA ELISA (10–920 ng/ml versus 2–500 ng/ml, respectively). There was no cross-reactivity with synthetic human and porcine pancreastatin (PST) in the two assays. There was a significant positive correlation between levels of CgA in sera from patients with carcinoid disease, measured by the two methods (r = 0.9, p < 0.0001), and the values were in the same range. Similarly, serum CgA levels in normal controls were also in the same range when assayed by the two methods. A commercially available porcine PST RIA method was evaluated, especially with respect to the influence of Sep-Pak extraction of serum on the levels of pancreastatin-like immunoreactivity (PST-LI). Ten sera from carcinoid patients were treated with Sep-Pak extraction, and levels of PST-LI were determined in non-extracted and extracted sera. There was a significant positive correlation between the concentrations of PST-LI measured in extracted and non-extracted carcinoid sera (r = 0.9, p < 0.002), and the levels were in the same range. There was also a significant positive correlation between levels of CgA and PST-LI in 49 carcinoid sera (r = 0.8, p< 0.0001). In the PST RIA there was a minimal cross-reactivity with human CgA (0.08%). In conclusion, we have found that the two immunoassays for measurement of CgA are sensitive and reproducible, and give similar results. Extraction of serum previous to assaying PST-LI seems not to be necessary.

Unique change of pancreastatin-like immunoreactivity in cerebrospinal fluid by aging

Using a specific antiserum for the C-terminal glycine amide region of human pancreastatin (PST), pancreastatin-like immunoreactivity (PST-LI) was measured in cerebrospinal fluid (CSF) from 447 subjects (368 ± 10.8 pmol/l, mean ± S.E.M.) free from endocrine diseases. The CSF contents of PST-LI showed a mountain-shape type change which peaked at 40 years of age. The highest concentration was found in the group of ages 40–49 years old (412 ± 22.9 pmol/l) and the lowest concentration was found in the group of ages 80–89 years old (293.2 ± 45.2 pmol/l) among various age groups. Gel chromatographic examination revealed the presence of two major forms (MW 13,500 and 5,400) of PST-LI in CSF. Because of the character of this antibody, the large molecular form is possibly an N-terminally elongated PST and the other may be PST-52. This may be the first report on the unique age-related change of PST concentration in CSF.

Chromogranin A(210–301) is the major form of pancreastatin-like material in human gut extracts and endocrine tumors

A radioimmunoassay of human pancreastatin was developed using a rabbit antiserum that selectively recognized the C- terminal amidated end of the peptide, and it was used for the identification of the molecular forms of pancreastatin in human gut (stomach, duodenum, small intestine, colon) and endocrine tumor extracts (liver metastasis of a gastrinoma and a medullary carcinoma of thyroid, one nonsecreting pancreatic tumor, one recurrence of a gut carcinoid, one vipoma and one insulinoma). In all gut extracts, a gel filtration chromatography revealed the presence of three peaks of pancreastatin-like immunoreactivity. The predominant form eluted with an apparent molecular weight higher than that of pancreastatin. This form was also predominant in the endocrine tumors analyzed, except in the insulinoma, where a lower molecular weight form predominated. The high molecular form was further purified from a liver metastasis of a gastrinoma. The pancreastatin-like immunoreactivity eluted in all the chromatographical systems (reverse-phase, ion exchange) as a single peak that was finally purified to homogeneity and sequenced. The sequence of the first 29 N- terminal amino acids was obtained unambiguously and corresponded to the sequence 210–238 of chromogranin A. Considering the selectivity of the assay used for peptide identification, this major form was identified as the fragment 210–301 of chromogranin A. It is likely that the predominant form of pancreastatin in human gut extracts and noninsular tumors is a 92 amino acid peptide.

Chromogranin A and pancreastatin-like immunoreactivity in human carcinoid disease

Objective: To evaluate chromogranin A (CgA) and pancreastatin-like immunoreactivity (PST-LI) as tumor markers in human carcinoid disease, compared with urinary excretion of 5-hydroxyindole acetic acid (5-HIAA), and to evaluate their role as indicators of survival. Patients and methods: Urinary 5-HIAA excretion was determined by a spectrophotometric method, while serum CgA and PST-LI were determined by radioimmunoassay methods in 38 patients with midgut, 10 with foregut and one with hindgut carcinoids. Results: In midgut carcinoid patients levels of 5-HIAA, CgA and PST-LI were raised by 76, 82 and 76%, respectively. The median CgA level in midgut carcinoid patients was significantly higher than in the controls (193 compared with 12ng/ml; P<0.01). In the midgut carcinoid patients, the median CgA value was significantly higher in women who died (1990 ng/ml) than in those who survived (46ng/ml; P<0.01), and significantly higher than in men, either survivors or non-survivors. The median PST-LI value was significantly higher in midgut carcinoid patients than in the control group (2282 compared with 33 pg/ml; P< 0.01). In women, the median PST-LI level was significantly higher in non-survivors than in survivors (9088 compared with 1337 pg/ml; P<0.01), and significantly higher than in male survivors and non-survivors. In foregut carcinoid patients, levels of CgA, PST-LI and 5-HIAA were increased in nine, eight and one patient, respectively. The median CgA and PST-LI levels in the foregut group were similar to the midgut group. Conclusion: CgA and PST-LI are useful markers in the diagnosis of both midgut and foregut carcinoids. They are as good as, or more sensitive than, 5-HIAA.

Chromogranin a and Pancreastatin-Like Immunoreactivity in Serum of Gastrinoma Patients

Gastrin and pancreastatin-like immunoreactivity were determined by radioimmunoassay methods and chromogranin A was determined by enzyme-linked immunoassay in sera from 18 patients with gastrinomas (Zollinger-Ellison syndrome) and in 20 age and sex matched controls. Gastrin serum levels in the gastrinoma patients were in the range 26-80,000 pmol/l, and in the controls 5-31 pmol/l. Chromogranin A serum levels in the gastrinoma group were in the range 6-2,700 ng/ml (mean +/- SEM: 400 +/- 147 ng/ml). The mean value of chromogranin A was significantly higher than in the control group (8 +/- 2 ng/ml, p = 0.008). The serum levels of pancreastatin-like immunoreactivity in the gastrinoma patients were in the range 23-1,994 pg/ml (597 +/- 123 pg/ml). The mean value of pancreastatin-like immunoreactivity in the gastrinoma group was significantly higher than in the control group (104 +/- 25 pg/ml, p = 0.0002). The levels of chromogranin A and pancreastatin-like immunoreactivity were significantly higher in patients with verified metastatic disease (p = 0.04, p = 0.01 respectively). There was a significantly positive correlation between levels of gastrin and pancreastatin-like immunoreactivity (r = 0.7, p = 0.002), while no correlation was found between gastrin and chromogranin A levels or between levels of chromogranin A and pancreastatin-like immunoreactivity. The study demonstrates an elevation of both chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. The lack of correlation between gastrin and chromogranin A, however, gives an indication that the gastrinoma cells are not the main source of serum chromogranin A elevation.

Distribution and coexistence of chromogranin A-, serotonin-and pancreastatin-like immunoreactivity in endocrine-like cells of the human anal canal

The comparative distribution and coexistence of chromogranin A (CGA)-, serotonin (5-hydroxytryptamine; 5-HT)- and pancreastatin (PST)-like immunoreactivity in endocrine-like cells of the human anal canal was investigated by light-microscopic immunocytochemistry. The largest population of colorectal endocrine-like cells consisted of CGA-immunoreactive (ir) cells, followed by the 5-HT-ir and PST-ir cell population. In the anal transitional zone (ATZ), CGA- and 5-HT-immunoreactivity was equally distributed; ir-PST was confined to a smaller endocrine-like cell population. In the squamous zone and the perianal skin, Merkel cells in the basal layer of the epidermis and hair follicles exhibited ir-CGA and ir-PST but no ir-5-HT. Double immunofluorescence on identical sections revealed distinct coexistence patterns. In the colorectal zone, about 2/3 of the CGA-ir endocrine-like cells also stained for 5-HT, whereas in the ATZ epithelium, CGA- and 5-HT-immunoreactivity completely overlapped. No 5-HT-immunoreactivity could be detected in CGA-ir Merkel cells of the squamous zone of the anal canal and the perianal skin. PST-immunoreactivity was present in about 1/3 of the CGA-ir colorectal and anal transitional endocrine-like cells and in about 1/4 of the Merkel-cell population staining for CGA. These chemically heterogeneous phenotypes of the anal endocrine-like and Merkel cells may reflect a specific regulatory role of these cells in the various epithelial linings of the human anal canal and the perianal skin.

Production of pancreastatin-like immunoreactivity, a presumed processing product of chromogranin A, in small cell lung carcinoma : Iguchi H, Funakoshi A, Tateishi K, Ichinose Y, Hara N, Ohta M. Department of Biochemistry, National Kyushu Cancer Center, Fukuoka 815. Cancer J 1990;3:197–201

Production of pancreastatin-like immunoreactivity, a presumed processing product of chromogranin A, in small cell lung carcinoma : Iguchi H, Funakoshi A, Tateishi K, Ichinose Y, Hara N, Ohta M. Department of Biochemistry, National Kyushu Cancer Center, Fukuoka 815. Cancer J 1990;3:197–201

Pancreatic Release of Pancreastatin in the Pig

It is known that pancreastatin-like immunoreactivity (PLI) occurs in the secretory granules of the islet B- and D-cells in the pig pancreas, and that porcine pancreastatin inhibits insulin secretion in rats and mice. In this study, we characterized the porcine plasma PLI and examined whether PLI is released from the pig pancreas in vivo. We found that PLI in unextracted pig plasma largely consists of two high-molecular fractions, with Mr values of 80-85,000 and 300-350,000, respectively. In addition, a small peak of PLI eluted after gel filtration at the position of synthetic porcine pancreastatin. After extraction on octadecylsilyl silica, virtually all PLI disappeared except in the fraction co-eluting with porcine pancreastatin. In thiopenthal-anesthetized pigs, plasma samples were obtained from the carotid artery and the superior pancreaticoduodenal vein. By multiplying the venous-arterial concentration difference by the pancreatic venous plasma flow, a net pancreatic output of PLI of 420 +/- 120 pmol/min was found. This pancreatic PLI output was significantly reduced by electrical stimulation of the local autonomic nerves along the superior artery during atropine administration (p less than 0.001). Furthermore, the pancreatic venous PLI levels were elevated during intravenous infusion of glucose (p less than 0.01). We conclude that pig plasma PLI levels can be measured by radioimmunoassay after extraction on octadecylsilyl silica and that there is a net pancreatic output of PLI, which is reduced by sympathetic stimulation and enhanced during hyperglycemia.

Pancreastatin-like immunoreactivity in human carcinoid disease

Pancreastatin-like immunoreactivity has been demonstrated in human carcinoid tumors by immunohistochemistry and radioimmunoassay, employing antisera raised to a synthetic C-terminal fragment of porcine pancreastatin. Immunohistochemistry revealed intense immunoreactivity in all tumors. By radioimmunoassay, high concentrations of pancreastatin-like immunoreactivity were measured in carcinoid tumors arising from the fore-gut (mean ± S.D. and range: 369 ± 955 and 9.4–3670 pmol g −1, respectively, n = 14), mid gut (mean ± S.D. and range: 1354 ± 1538 and 337–3978 pmol g −1, respectively, n = 5) and in metastases associated with mid-gut tumors (mean ± S.D. and range: 684 ± 739 and 31–2255 pmol g −1, respectively, n = 7), compared to corresponding normal tissues (< 1.4 pmol g −1). Individuals with hepatic metastases and carcinoid syndrome had elevated circulating levels of pancreastatin-like immunoreactivity (mean ± S.D. and range: 770 ± 1249 and 42–4120 pmol l −1; n = 12), significantly above the normal, fasting range (mean ± S.D. and range: 14.9 ± 7.5 and 4–37.5 pmol l −1, respectively, n = 42). However, patients with non-metastatic carcinoid tumors ( n = 4), who had been clinically cured after primary tumor resection, had plasma levels within the normal range. Chromatographic analysis of extracts of primary lung and ileal tumors, hepatic metastases from ileal tumors and plasma from individuals with carcinoid syndrome revealed molecular heterogeneity of pancreastatin-like immunoreactivity.

Pancreastatin-Like Immunoreactivity in Urine

The concentration and molecular form of pancreastatin-like immunoreactivity (PST-LI) in urine of normal subjects and patients with noninsulin-dependent diabetes mellitus or chronic renal failure were examined. PST-LI output (mean +/- SEM) in urine of normal subjects was 74.6 +/- 8.5 pmol/day and 87.1 +/- 11.7 pmol/g creatinine. That in patients with noninsulin-dependent diabetes mellitus was 78.1 +/- 9.0 (SEM) pmol/day and 85.6 +/- 9.0 pmol/g creatinine and was not significantly different from that in normal subjects. Gel filtration analysis showed that PST-LI molecules excreted in urine of these two groups were smaller than human pancreastatin (43-52) (hPST-10) of C-terminal fragment. The PST-LI molecular forms were deduced to be nonbioactive from the result that hPST-10 did not inhibit pancreatic exocrine secretion. PST-LI excretion in patients with chronic renal failure was 258.5 +/- 62.9 pmol/day and 713.2 +/- 219.6 pmol/g creatinine. A molecular form corresponding to hPST-52 and a larger form eluted in the high mol wt region (approximately mol wt 15 K) were detected by gel filtration of urine from these patients, indicating that PST-LI is excreted in urine without degradation in patients with chronic renal failure. These results support the suggestion that the kidney may play an important role in PST degradation or metabolism.

Distribution and partial characterisation of immunoreactivity to the putative C-terminus of rat pancreastatin

The presumptive C-terminal nonapeptide of rat pancreastatin was synthesised based upon the sequence of rat chromogranin A (CGA) analogous to that of porcine pancreastatin as contained within porcine CGA. Antisera were produced which were used to determine the qualitative and quantitative distribution of pancreastatin-like immunoreactivity in rat tissues by immunocytochemistry and radioimmunoassay respectively. Pancreastatin-like immunoreactivity was most abundant in pituitary, adrenal, gastric corpus and thyroid with considerably lower levels detected in the remainder of the gastroentero-pancreatic system and brain. Immunoreactivity was localised exclusively in endocrine cells and the relative abundance of immunoreactive cells paralleled the levels obtained radioimmunometrically. Chromatographic characterisation of pancreastatin-like immunoreactivity revealed molecular heterogeneity. Immunoreactive peptides of similar size to synthetic rat pancreastatin were present in gastrointestinal tissues and thyroid. These data indicate a tissue specific processing of CGA in the rat.