Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake.

Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43 nM in static settings and 2.4 µM in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested ß-lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.

Does the MMR vaccine and secretin or its receptor share an antigenic epitope?

In a subgroup of children with autism-spectrum like conditions symptoms seem to appear as a 'regression' (in normal development). It has been postulated that the onset of such autistic symptoms may involve an autoimmune response against the central nervous system and that the antigenic determinant could possibly be gastrointestinal in origin. It has been suggested that the presence of the measles virus and 'autistic enterocolitis' demonstrates the possibility that the MMR triple vaccine may be mediating the inflammation with possible production of antibodies against the virus containing vaccine. Such an antibody may share antigenic determinant to molecules found in the gut. We propose that this may be secretin or its receptor, found in the gut as well as in the central nervous system. The antibody response to the gut may also conceivably occur in the brain at a critical time in development. The modulation of development by secretin may be a static event possibly occurring at a specific time in early childhood development and if it involves an autoimmune response then a disruption in development may result. These hypothesized events can only occur if the MMR vaccine shares antigenic determinants that resemble secretin or any of its receptor types and remains to be studied.

What may be the anatomical basis that secretin can improve the mental functions in autism?

Autism was first described and characterized as a behavioral disorder more than 50 years ago. The major abnormality in the central nervous system is a cerebellar atrophy. The characteristic histological sign is a striking loss or abnormal development in the Purkinje cell count. Abnormalities were also found in the limbic system, in the parietal and frontal cortex, and in the brain stem. The relation between secretin and autism was observed 3 years ago. Clinical observations by Horváth et al. [J. Assoc. Acad. Minor. Physicians 9 (1998) 9] supposed a defect in the role of secretin and its receptors in autism. The aim of the present work was to study the precise localization of secretin immunoreactivity in the nervous system using an immunohistochemical approach. No secretin immunoreactivity was observed in the forebrain structures. In the brain stem, secretin immunoreactivity was observed in the mesencephalic nucleus of the trigeminal nerve, in the superior olivary nucleus, and in scattered cells of the reticular formation. The most intensive secretin immunoreactivity was observed in the Purkinje cells of the whole cerebellum and in some of the neurons of the central cerebellar nuclei. Secretin immunoreactivity was also observed in a subpopulation of neurons in the primary sensory ganglia. This work is the first immunohistochemical demonstration of secretin-immunoreactive elements in the brain stem and in primary sensory ganglia.

Liver transplantation restores endocrine cells in patients with familial amyloidotic polyneuropathy.

BACKGROUND: The aim of this study was to investigate familial amyloidotic polyneuropathy, Portuguese type patients' endocrine cell content in the stomach and duodenum before and after liver transplantation, and to relate the findings to the patients' gastrointestinal disturbances. METHODS: Ten liver-transplanted familial amyloidotic polyneuropathy, Portuguese type patients and 10 healthy controls were seen. Endocrine cells were identified by immunohistochemistry and quantified with computerized image analysis. The activity of the cells was appraised by measurements of the cell secretory index and nuclear area. Clinical symptoms were obtained from the patients' medical records. RESULTS: After transplantation, a significant increase of several endocrine cell types were noted, and the pretransplant depletion of several types of endocrine cells disappeared. For no type of endocrine cell was any difference compared with controls noted after transplantation. There was no significant decrease of the amount of amyloid in the biopsies after liver transplantation. The patients' symptoms remained generally unchanged after transplantation, although a substantial time lapse between pretransplant evaluation and transplantation was present. CONCLUSIONS: Liver transplantation restores the endocrine cells in the upper part of the gastrointestinal tract. The restoration was not correlated with an improvement of the patients' symptoms. No decrease of the amyloid deposits was noted.

An immunohistochemical study of endocrine cells in the alimentary tract of the red-bellied frog, Bombina orientalis.

The regional distribution and relative frequency of endocrine cells was studied immunohistochemically (PAP method) in the alimentary tract of the red-bellied frog, Bombina orientalis, using antisera against serotonin, somatostatin, chromogranin (CG), cholecystokinin (CCK)-8, bombesin, secretin, glucagon and pancreatic polypeptide (PP). Eight kinds of endocrine cells were identified in this study. These immunoreactive cells were located in the gastric glands of the stomach regions and in the intestinal or esophageal epithelium with variable frequencies. They were spherical or spindle-shaped. Serotonin- and somatostatin-immunoreactive cells were demonstrated in the whole alimentary tract including esophagus. CG-immunoreactive cells were restricted to the stomach. CCK-8-immunoreactive cells were observed from the antrum to the ileum. Bombesin-immunoreactive cells were restricted to the stomach. Secretin-immunoreactive cells were demonstrated in the pylorus, duodenum and ileum. Glucagon-immunoreactive cells were found in the antrum and duodenum. PP-immunoreactive cells were detected from the antrum to the rectum. In conclusion, throughout the alimentary tract of the red-bellied frog, the different regional distribution and relative frequency of endocrine cells were demonstrated. The regional distributions and relative frequencies of the endocrine cells in the alimentary tract of the red-bellied frog were resembled to those of the other anuran species except for esophagus.

Inhibition of gastric acid secretion in rat stomach by PACAP is mediated by secretin, somatostatin, and PGE(2).

Pituitary adenylate cyclase-activating polypeptide (PACAP), existing in two variants, PACAP-27 and PACAP-38, is found in the enteric nervous system and regulates function of the digestive system. However, the regulatory mechanism of PACAP on gastric acid secretion has not been well elucidated. We investigated the inhibitory action of PACAP-27 on acid secretion and its mechanism in isolated vascularly perfused rat stomach. PACAP-27 in four graded doses (5, 10, 20, and 50 microg/h) was vascularly infused to determine its effect on basal and pentagastrin (50 ng/h)-stimulated acid secretion. To study the inhibitory mechanism of PACAP-27 on acid secretion, a rabbit antisecretin serum, antisomatostatin serum, or indomethacin was administered. Concentrations of secretin, somatostatin, PGE(2), and histamine in portal venous effluent were measured by RIA. PACAP-27 dose-dependently inhibited both basal and pentagastrin-stimulated acid secretion. PACAP-27 at 10 microg/h significantly increased concentrations of secretin, somatostatin, and PGE(2) in basal or pentagastrin-stimulated state. The inhibitory effect of PACAP-27 on pentagastrin-stimulated acid secretion was reversed 33% by an antisecretin serum, 80.0% by an antisomatostatin serum, and 46.1% by indomethacin. The antisecretin serum partially reduced PACAP-27-induced local release of somatostatin and PGE(2). PACAP-27 at 10 microg/h elevated histamine level in portal venous effluent, which was further increased by antisomatostatin serum. However, antisomatostatin serum did not significantly increase acid secretion. It is concluded that PACAP-27 inhibits both basal and pentagastrin-stimulated gastric acid secretion. The effect of PACAP-27 is mediated by local release of secretin, somatostatin, and PGE(2) in isolated perfused rat stomach. The increase in somatostatin and PGE(2) levels in portal venous effluent is, in part, attributable to local action of the endogenous secretin.

Co-localization of neuroendocrine hormones in the human fetal pancreas.

OBJECTIVE AND DESIGN: Co-localization of the four major pancreatic hormones, and also of islet amyloid polypeptide (IAPP), peptide tyrosine tyrosine (PYY), secretin and neurotensin, has been studied in the endocrine pancreas of human fetuses at 16, 18 and 22 weeks of gestation. METHODS: Double and triple immunofluorescence stainings have been used. RESULTS: All three fetal pancreata contained cells that showed insulin, glucagon, somatostatin, pancreatic polypeptide (PP), IAPP, secretin and PYY immunoreactivity. Neurotensin cells were found in the youngest fetus and gastric inhibitory polypeptide (GIP) in the two older fetuses. Co-localization of two hormones occurred in most of the endocrine cell types in the three fetuses examined, but three hormones occurred in only a few cells and especially in the youngest fetus. Somatostatin cells were the only cell type which was largely monohormonal. Our findings showed that there are two different co-localization patterns: insulin was co-localized mainly with IAPP and glucagon, while secretin and PYY occurred together with glucagon and PP. CONCLUSIONS: These data are the first to describe secretin and neurotensin in the fetal pancreas. Two different co-localization patterns could be distinguished: insulin, IAPP and glucagon, and glucagon, secretin, PP and PYY.

Canine pancreatic juice stimulates the release of secretin and pancreatic secretion in the dog.

A secretin-releasing factor (SRF) was found in canine pancreatic juice that increases plasma secretin and stimulates pancreatic secretion in rats, suggesting that a positive feedback mechanism may be involved in the regulation of pancreatic secretion. In the present study, we investigated to determine whether or not SRF releases endogenous secretin and stimulates exocrine pancreatic secretion in conscious dogs. Fresh pancreatic juice was collected from four dogs by intravenous administration of secretin at 0.5 microg. kg(-1). h(-1) and CCK at 0.2 microg. kg(-1). h. The juice was boiled for 10 min at 100 degrees C. Experiments were carried out in phase I of spontaneous cycle of interdigestive pancreatic secretion. The testing solutions were infused intraduodenally in separate experiments: NaHCO3 solution (0.1 M, 4.5 ml/min, 60 min), a corn oil (Lipomul, 2 ml/min, 10 min), boiled pancreatic juice (BPJ, 4.5 ml/min, 60 min), and mixture of BPJ and Lipomul. Pancreatic secretion of fluid and bicarbonate was significantly increased by either BPJ or a mixture of BPJ and Lipomul (34- and 31-fold or 41- and 38-fold, respectively). Plasma secretin level also significantly increased by 164.7 +/- 13.4% and 223.1 +/- 35.0%, respectively, from basal concentration of 1.7 +/- 0.5 pM. In contrast, neither bicarbonate solution nor Lipomul influenced the plasma secretin level or pancreatic secretion. In addition, when Lipomul was incubated with BPJ, no fatty acid was produced. Thus the increased pancreatic secretion in the dog infused with a combination of BPJ and Lipomul was caused by SRF in BPJ, which released endogenous secretin. Moreover, the increases by BPJ of both plasma secretin level and bicarbonate secretion were completely blocked by intravenous administration of an antisecretin antibody in these dogs. The observations suggest that SRF in pancreatic juice exerts a positive feedback effect on exocrine pancreatic secretion that is mediated by the release of secretin in the interdigestive state in dogs.

Duodenal acid-induced gastric relaxation is mediated by multiple pathways.

In this study, we used an in vivo anesthetized rat model to investigate the mechanisms responsible for duodenal acid-induced inhibition of gastric motility. Intraduodenal infusion of HCl produced a rate-dependent decrease in intragastric pressure. Infusion of HCl at 2 ml/h produced a physiological plasma secretin level and elicited a decrease in intragastric pressure of 3.0 +/- 0. 2 cmH20. Infusion of rabbit secretin antiserum reduced the acid-induced inhibition of gastric motility by 85 +/- 5%, suggesting mediation mainly by endogenous secretin. Administration of the cholecystokinin (CCK)-A antagonist MK-329 caused only a modest 10 +/- 3% reduction in gastric relaxation, whereas the serotonin antagonist ICS-205930 had no effect. In contrast, immunoneutralization with the secretin antibody caused only a 15% reduction in the relaxation evoked by a higher rate of HCl infusion (3 ml/h), whereas MK-329 and ICS-205930 caused a 20 +/- 4% reduction and no reduction, respectively. Bilateral truncal vagotomy or perivagal application of capsaicin completely abolished gastric relaxation in response to low rates (1-2 ml/h) of 0.1 N HCl infusion but only partially affected gastric relaxation in response to a higher infusion rate (3 ml/h). These observations indicate that multiple pathways mediate the duodenal acid-induced inhibition of gastric motility. At low rates of HCl infusion, gastric relaxation is mediated primarily by endogenous secretin, which acts through vagal afferent pathways. At higher rates of HCl infusion, gastric relaxation is mediated by endogenous secretin, CCK, and possibly by the direct action of HCl on vagal afferent pathways or yet unidentified neuropathways.

Secretin inhibits gastric acid secretion via a vagal afferent pathway in rats.

Secretin is an enterogastrone that inhibits gastric acid secretion and motility. Recently, it was reported that secretin inhibited gastric emptying via a capsaicin (Cap)-sensitive vagal afferent pathway. However, a possible role of the sensory afferent pathway in secretin-inhibited acid secretion has not been clarified. We investigated whether or not the acid secretion suppressed by secretin is modulated by a vagal and/or splanchnic afferent pathway in rats. Subdiaphragmatic perivagal (PV) or periceliac ganglionic (PCG) application of Cap (10 mg/ml) or vehicle was performed in both conscious and anesthetized rats 2 wk before experiments. Bilateral vagotomy was performed in some conscious rats 5 days before studies. Pentagastrin was administered intravenously at 0.6 microg . kg-1 . h-1. Secretin (20 pmol . kg-1 . h-1 iv) or 0.03 N HCl (4.32 ml/h id) was infused in conscious rats with gastric cannulas or anesthetized rats with ligation of the pylorus, respectively. A rabbit antisecretin serum was injected in some anesthetized rats before duodenal acidification. Secretin significantly inhibited pentagastrin-stimulated acid secretion by 63% (P < 0.01), which was abolished by both vagotomy and PV treatment of Cap in conscious rats. In anesthetized rats, duodenal infusion of 0.03 N HCl suppressed pentagastrin-induced acid secretion by 59.4% (P < 0.01), which was reversed not only by antisecretin serum but also by PV application of Cap. However, PCG treatment with Cap did not influence the inhibition by secretin or duodenal acidification in either awake or anesthetized rats. These results indicate that the inhibition by secretin of pentagastrin-stimulated acid secretion is mediated by a Cap-sensitive vagal afferent pathway but not via a splanchnic afferent pathway in rats.

Pituitary adenylate cyclase-activating peptide stimulates rat pancreatic secretion via secretin and cholecystokinin releases.

BACKGROUND & AIMS: Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates protein and/or amylase secretion from isolated rat pancreatic acini. The effect of PACAP on pancreatic secretion in vivo and its mechanism of action were studied. METHODS: Rats were prepared with pancreatic duct cannulation, pyloric ligation, and bile diversion into duodenum, and 2.5, 5, and 10 nmol/kg PACAP-27 was administered intravenously while pancreatic juice was collected for 30 minutes. In other groups of rats, the effect of 10 nmol/kg PACAP-27 was studied under the influence of either atropine; loxiglumide, an antisecretin serum; a combination of both loxiglumide and the antiserum; or a PACAP antagonist (PACAP 6-38). Plasma secretin and cholecystokinin concentrations were measured by radioimmunoassay. RESULTS: (1) PACAP dose-dependently increased pancreatic secretion of fluid, bicarbonate, and protein; (2) the increase in pancreatic secretion paralleled that of plasma secretin and cholecystokinin; (3) a combination of loxiglumide and antisecretin serum eliminated the PACAP-stimulated pancreatic secretion, whereas loxiglumide or antisecretin serum alone partially but significantly blocked pancreatic secretion; (4) atropine failed to influence PACAP-induced pancreatic secretion; and (5) PACAP antagonist profoundly suppressed the PACAP action. CONCLUSIONS: PACAP-27 dose-dependently stimulates pancreatic secretion of fluid, bicarbonate, and protein in rats. This effect is mediated by release of both secretin and cholecystokinin and is independent of cholinergic tone.

Pancreatic fluid hypersecretion in rats after acute pancreatitis.

Pancreatic exocrine function was examined in rats during the early stage of acute pancreatitis induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Basal pancreatic fluid secretion at 6 hr after the first of four cerulein injections was significantly elevated (27.6 +/- 3.7 vs 17.4 +/- 2.1 microliters/30 min in control, P < 0.01) and further increased with time, reaching the peak level at 24 hr (105.1 +/- 4.6 microliters/30 min). Intravenous infusion of loxiglumide (50 mg/kg body wt/hr), atropine (100 micrograms/kg body wt/hr), or anti-secretin serum did not modify the fluid hypersecretion observed at 24 hr after induction of acute pancreatitis. Loxiglumide, when given 30 min before the first cerulein injection, markedly reduced fluid secretion, but could not inhibit the fluid hypersecretion when applied after the last cerulein injection. Leakage of Evans blue dye into pancreatic juice was slightly but significantly increased in postpancreatitic rats compared with that in the control rats (1.30 +/- 0.17 vs 0.75 +/- 0.08 micrograms/ml, P < 0.01), whereas that in the pancreas was not different from the control rats. In vivo labeling with 5-bromo-2'-deoxyuridine showed active proliferation of acinar and ductular cells at 6 hr. In addition, the fluid was rich in chloride (137.1 +/- 2.5 at 24 hr vs 92.4 +/- 3.3 meq/liter in control, P < 0.01) but poor in bicarbonate concentration (39.0 +/- 2.0 at 24 hr vs 46.5 +/- 1.9 mmol/liter in control, P < 0.01), indicating acinar cell secretion. These results indicate that pancreatic fluid secretion during the early stage of acute pancreatitis induced by supramaximal doses of cerulein was markedly increased not by CCK-, secretin-, or cholinergic-dependent mechanisms but probably by acinar cell proliferation.

Sevenspan transmembrane molecules: novel receptors involved in leukocyte adhesion.

CD97 is a member of a new subgroup of seven-span transmembrane (7-TM) molecules which belong to the secretin receptor superfamily. Different from other members of the secretin receptor family, these recently characterized molecules have extended extracellular regions comprising several EGF domains near the NH2 terminus. We recently demonstrated that the extracellular part of CD97 is involved in intercellular adhesion since it specifically binds to CD55 (decay accelerating factor), a regulatory protein of the complement cascade. To our knowledge this is the first demonstration of a cellular ligand for a 7-TM molecule.

[Preparation of specific antiserum of secretin and its use in time-resolved fluoroimmunoassay].

We have prepared a specific anti-secretin antiserum and developed a sensitive time-relevant fluoroimmunoassay (TR-FIA) for secretin. An anti-secretin antiserum was produced in rabbit by immunization with synthetic secretin C-terminal 8 residue conjugate to chicken serum albumin as antigen. The TR-FIA was based on the competition between free secretin and biotinylated secretin as a tracer for rabbit anti-secretin antibodies on a goat anti-rabbit IgG antibody coated microtiter plate. After separation of bound and free fractions, a solution of europium (III) ion chelate labeled streptavidin (Eu-SA) was added to the biotinylated secretin bound on the microtiter plate. The microtiter plate was washed and then Eu-SA activity was measured by time-resolved fluorometry. In this TR-FIA, the measurable range of secretin was from 2.5 to 100 pg/assay and the specificity was less than 0.01% against other peptide hormones. For the measurement of secretin in the human plasma, a sample was required for the pretreatment in order to separate from interfering substances. The mean recovery of secretin using commercially reverse phase column was 80.2% (n = 11). The plasma secretin concentrations of normal subjects and those with various diseases could be measured by this proposed TR-FIA.

Cholinergic stimulatory effect of intragastric administration of a prostaglandin E2 analogue on pancreatic exocrine secretion in conscious rats.

The effect of a long-acting, potent synthetic analogue of prostaglandin E2, enprostil, on pancreatic exocrine secretion was examined in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice separately. Pancreatic exocrine secretion was increased by intragastric administration of enprostil but inhibited by its intravenous administration. The pancreatic response to intragastric administration of enprostil was not inhibited by the administration of cholecystokinin antagonist or secretin antibody, or by bilateral vagotomy, but was completely abolished by atropine. Therefore, intragastric administration of enprostil seemed to stimulate pancreatic exocrine secretion via a peripheral gastro-(entero)-pancreatic reflex.

Mediation of trypsin inhibitor-induced pancreatic hypersecretion by secretin and cholecystokinin in rats.

We investigated a hormonal mechanism in a trypsin inhibitor-induced pancreatic hypersecretion in rats. Intraduodenal administration of a synthetic trypsin inhibitor, camostat, resulted in significant increases in plasma concentration of both secretin and cholecystokinin in a dose-related manner that paralleled a significant increase in exocrine pancreatic secretion. To eliminate the effect of circulating secretin in rats, a rabbit antisecretin serum was given IV that resulted in a 77% reduction in bicarbonate secretion stimulated by intraduodenal camostat. A cholecystokinin receptor antagonist, MK-329, also inhibited significantly the camostat-induced increase in pancreatic secretion; volume and bicarbonate output were reduced by 35% each and amylase output by 73%. The combined administration of antisecretin serum and MK-329 completely abolished the pancreatic exocrine secretion stimulated by camostat. These observations indicate that the camostat-stimulated pancreatic exocrine secretion is mediated by the increased release of both secretin and cholecystokinin in rats.

Role of secretin in basal and fat-stimulated pancreatic secretion in conscious rats.

The role of endogenous secretin in basal and fat-stimulated pancreatic exocrine secretion was investigated in conscious rats. Rats were prepared with chronic fistulas draining bile and pancreatic juice, which was collected and returned to the duodenum at all times. Six days postoperative rats were fasted overnight, and pancreatic protein and fluid secretion were monitored for 3 h under basal conditions (0.15 M NaCl, intraduodenally) and during 2 h of intraduodenal infusion of a 20% triglyceride emulsion (Liposyn). Solutions were infused at 4.6 ml/h. Rats received a single bolus injection of 0.1 ml antisecretin serum or normal rabbit serum starting in the second hour of the basal period, and the effect on basal and fat-stimulated pancreatic protein and fluid secretion was determined. Antisecretin serum significantly inhibited basal interdigestive pancreatic protein and fluid secretion by 43% and 36%, respectively. Infusion of 20% fat emulsion stimulated a 2.1-fold increase in pancreatic protein and fluid secretion. The stimulation of both protein and fluid secretion was significantly inhibited by 60% by antisecretin serum. Plasma secretin after 2 h of fat infusion was 17.7 +/- 1.8 pM and was greatly reduced by the presence of secretin antiserum. The results support the hypothesis that secretin released by fatty acids is an important mediator of the pancreatic protein and fluid secretory response to dietary fat in the rat.

[Inhibitory effect of secretin on gastric motility in isolated vascular perfused rat stomach].

Effect of secretin on gastric motility was studied on the preparation of isolated vascular perfused rat stomach. The results showed: (1) Secretin markedly inhibited spontaneous as well as pentagastrin stimulated antral motility. (2) Antisecretin serum completely abolished the inhibitory effect of secretin on antral motility. (3) Antisomatostatin serum and indomethacin blocked the inhibitory effect on antral motility induced by secretin. The results indicated that the inhibitory effect of secretin might be produced through direct action of secretin on secretin receptors and mediated partially by the local somatostatin and prostaglandin in gastric antrum.

Ultrastructural identification of human secretin cells by the immunogold technique. Their costorage of chromogranin A and serotonin.

We have localized secretin in a morphologically distinctive endocrine cell scattered in the epithelium covering the villi and uppermost crypts of the human duodenum and jejunum. The human secretin cell was characterized by relatively large (mean diameter 299 nm +/- 69 SD), fairly irregular granules, the majority of which showed homogeneous distribution of secretin and chromogranin A immunolabelling in a structurally homogeneous core. Other granules had a targetoid pattern due to an inner, argyrophobe, secretin-immunoreactive body surrounded by an argyrophil, chromogranin A immunoreactive mantle. These targetoid granules represent a distinctive ultrastructural marker of the secretin cell. Secretin cell granules have been shown to react with chromogranin A antibodies and Grimelius' silver, while lacking chromogranin B immunoreactivity. About 1/3 of secretin cells also showed serotonin immunostaining.