Immunoneutralization Of Somatostatin Research Articles

Cholecystokinin inhibits gastrin secretion independently of paracrine somatostatin secretion in the pig

Background: Cholecystokinin inhibits the secretion of gastrin from antral G cells, an effect that is speculated to be mediated by D cells secreting somatostatin. The aim of the study was to test directly whether cholecystokinin inhibition of antral gastrin secretion is mediated by somatostatin. Methods: The effects of CCK on gastrin and somatostatin secretion were studied in isolated vascularly perfused preparations of pig antrum before and after immunoneutralization brought about by infusion of large amounts of a high affinity monoclonal antibody against somatostatin. Results: CCK infusion at 10−9 M and 10−8 M decreased gastrin output to 70.5% ± 7.6% (n = 8) and 76.3% ± 3.6% (n = 7) of basal output, respectively. CCK at 10−10 M had no effect (n = 6). Somatostatin secretion was dose‐dependently increased by CCK infusion and increased to 268 ± 38.2% (n = 7) of basal secretion during infusion of CCK at 10−8 M. Immunoneutralization of somatostatin caused a doubling of the basal secretion of gastrin, but did not affect the CCK‐induced decrease in gastrin secretion. Conclusion: CCK inhibits gastrin secretion independently of paracrine somatostatin secretion.

Activation of somatostatin receptor subtype 2 inhibits insulin secretion in the isolated perfused human pancreas.

Five distinct somatostatin receptors (SSTRs) have been cloned, characterized, and designated SSTRs 1-5. The role of these receptors in B-cell signaling has not been well characterized. In the current study, the isolated perfused human pancreas model was used to determine the specific effect of 4 different somatostatin receptor agonists on insulin secretion. We demonstrated that the SSTR 2 agonist and octreotide significantly suppressed insulin secretion. Furthermore, even during the immunoneutralization of endogenous intrapancreatic somatostatin, the SSTR 2 agonist was able to reverse the effect of somatostatin immunoneutralization by suppressing insulin secretion. These results demonstrate that activation of SSTR 2 suppresses insulin secretion in the isolated perfused human pancreas.

Neurotransmitters mediating the intestinal peristaltic reflex in the mouse.

The motor, modulatory, and sensory neurotransmitters that mediate the peristaltic reflex in the mouse colon were identified by direct measurement, and their involvement in various pathways was determined by selective receptor antagonists. Mucosal stimulation in the central compartment of a three-compartment flat sheet preparation of mouse colon elicited ascending contraction and descending relaxation in the orad and caudad compartments, respectively. Ascending contraction was accompanied by substance P release, a marker for excitatory neurotransmitter release, into the orad compartment and was partly inhibited by atropine and spantide, and abolished by a combination of the two antagonists. Descending relaxation was accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release, into the caudad compartment, and was partly inhibited by VIP10-28 and NG-nitro-L-arginine, and abolished by a combination of the two agents. Somatostatin release increased during descending relaxation: immunoneutralization of somatostatin or blockade of its effect with a selective somatostatin type 2 receptor antagonist inhibited descending relaxation. The delta-opioid receptor antagonist naltrindole augmented descending relaxation and ascending contraction. Calcitonin gene-related peptide (CGRP) release increased in the central compartment and was mediated by concurrent release of 5-hydroxytryptamine (5-HT) because its release was blocked by a 5-HT4 receptor antagonist. Both the latter and the CGRP antagonist CGRP8-37, inhibited ascending contraction and descending relaxation. Thus, the reflex in mouse like that in rat and human intestine is initiated by mucosal release of 5-HT and activation of 5-HT4 receptors on CGRP sensory neurons and is relayed via somatostatin and opioid interneurons to VIP/nitric-oxide synthase inhibitory motor neurons and via cholinergic interneurons to acetylcholine/tachykinin excitatory motor neurons.

Effects of administration of somatostatin‐14 and immunoneutralization of somatostatin on endocrine and growth responses in rainbow trout

Injection of somatostatin‐14 (SS‐14) at 5 ng g−1 body mass (BM) into rainbow trout Oncorhynchus mykiss decreased (P < 0·05, cubic, r2 = 0·54) levels of growth hormone (GH) (1·5 ± 0·9 ng ml−1v. 6·6 ± 0·6 ng ml−1) over time when compared to controls. Somatostatin‐14 at 50 ng g−1 BM also decreased (P = 0·064, quadratic; r2 = 0·30) levels of GH (3·6 ± 2·1 ng ml−1v. 6·6 ± 0·6 ng ml−1) over time compared to controls. In a second study, passive immunization against SS‐14 (1 : 25 dose) increased (P = 0·10, cubic, r2 = 0·12) levels of GH (11·0 ± 4·8 ng ml−1v. 5·2 ± 1·4 ng ml−1) over time. Passively immunizing against SS‐14 (1 : 50 dose) increased (P < 0·05, cubic, r2 = 0·10) levels of GH (8·2 ± 2·3 ng ml−1v. 5·2 ± 1·4 ng ml−1) over time compared to controls. Overall, in the active immunization study there was no difference (P > 0·10) in specific growth rate (G) or feed conversion ratio (FCR) between the three treatment groups during the 9 weeks of the study. Only four of the fish immunized against SS‐14, however, developed antibody titres against SS. Compared to controls, these fish exhibited a G of 0·89 ± 0·09 v. 0·56 ± 0·09% per 3 weeks and FCR of 0·80 ± 0·04 v. 1·20 ± 0·05 g g−1. In SS‐14 immunized fish, levels of GH decreased (P < 0·05) by day 63 while levels of insulin like growth factor‐I (IGF‐I) increased (P < 0·05) by day 42 and 63. These results indicate the hypothalamic hormone SS‐14 regulates GH secretion similarly in rainbow trout as it does in mammals. Active immunization against SS‐14 could improve growth performance in rainbow trout but enhanced G and FCR is dependent upon generation of antibody titres.

Somatostatin receptor type 2 mediates bombesin-induced inhibition of gastric acid secretion in mice.

Studies in isolated mouse stomach showed that bombesin releases somatostatin. We characterized the effects of exogenous bombesin on gastric acid secretion in mice and determined the involvement of somatostatin and somatostatin receptor type 2 (SSTR2) by using somatostatin immunoneutralization, the SSTR2 antagonist, PRL-2903, and SSTR2 knockout mice. Gastric acid secretion was monitored under basal and pentagastrin-, histamine- or bethanechol-stimulated conditions in urethane-anaesthetized mice. Bombesin (10-40 micro g kg-1 h-1) and somatostatin-14 (20 micro g kg-1 h-1) were infused I.V. 10 and 30 min after PRL-2903 or somatostatin antibody pretreatment, respectively. Urethane-anaesthetized wild-type mice had low basal acid secretion (0.12 +/- 0.01 micro mol (10 min)-1) compared with SSTR2 knockout mice (1.43 +/- 0.10 micro mol (10 min)-1). Somatostatin antibody and PRL-2903 increased basal secretion in wild-type mice but not in SSTR2 knockout animals. In wild-type mice, bombesin inhibited secretagogue-stimulated acid secretion in a dose-dependent manner, and somatostatin-14 inhibited pentagastrin-stimulated secretion. In wild-type mice pretreated with somatostatin antibody or PRL-2903 and in SSTR2 knockout mice, bombesin and somatostatin-14 I.V. infusion did not alter the increased gastric acid secretion. These results indicate that, in mice, bombesin inhibits gastric acid secretion through the release of somatostatin and the activation of SSTR2. These observations strengthen the important role of SSTR2 in mediating somatostatin inhibitory actions on gastric acid secretion.

Immunoneutralization of somatostatin, insulin, and glucagon causes alterations in islet cell secretion in the isolated perfused human pancreas.

In this study, immunoneutralization of endogenous insulin, glucagon, and somatostatin with specific antibodies was used in an isolated perfused human pancreas (IPHP) model. To study intrapancreatic cellular interactions and pancreatic hormonal secretion. Randomized, sequential 10-minute test intervals of single-pass perfusion with each antibody were performed at 3.9 mM or 11.5 mM steady-state glucose concentrations. Somatostatin, insulin, and glucagon levels were measured in the effluent during basal and immunoneutralization intervals. At 3.9 mM glucose concentration, somatostatin antibody (SS-Ab) stimulated insulin and glucagon secretion, insulin antibody (IN-Ab) inhibited glucagon secretion, and glucagon antibody (GN-Ab) stimulated insulin secretion. At 11.5 mM glucose concentration, SS-Ab stimulated insulin secretion, IN-Ab stimulated glucagon and inhibited somatostatin secretion, and GN-Ab stimulated insulin secretion. The variation in hormonal responses to immunoneutralization during stimulated and nonstimulated glucose conditions suggests that a dynamic association exists between the pancreatic cells.

Active immunoneutralization of somatostatin in the sheep: effects on gastrointestinal somatostatin expression, storage and secretion

In the absence of somatostatin antagonists, somatostatin antisera administered acutely or animals chronically immunized against somatostatin have been used to define the functions of somatostatin. However, the circulating immunoglobulins from immunized animals may contain substantial quantities of endogenous hormones. This has not been examined for somatostatin. We have measured the amount of free somatostatin bound to circulating immunoglobulins in somatostatin-immunized animals and the effect of this sequestering of the free peptide on somatostatin secretion and gastric somatostatin synthesis and storage. The average concentration of somatostatin bound to the antisera was 6.9 nmol/l, about 1000-fold higher than normal circulating levels. Compared to control animals, there was a doubling of somatostatin mRNA in the fundus and a 4-fold increase in fundic somatostatin peptide. Similar increases were seen in pancreas, but the antrum was not significantly affected providing further evidence of distinct regulatory mechanisms between the antrum and fundus. We suggest that withdrawal of active somatostatin activates a regulatory loop to increase fundic somatostatin biosynthesis and storage. The data support the concept that somatostatin autoregulates its own expression at both the RNA and peptide level.

Can GHRH or GH secretagogues re-initiate pituitary GH pulsatility?

Can GHRH or GH secretagogues re-initiate pituitary GH pulsatility?

Prostaglandins inhibit secretion of histamine and pancreastatin from isolated rat stomach ECL cells.

1. The present study examines the effect of naturally occurring prostanoids and prostaglandin (PG) congeners on gastrin- and pituitary adenylate cyclase-activating peptide (PACAP)-evoked histamine and pancreastatin secretion from isolated rat stomach ECL cells. 2. ECL cells (75-85% purity) were isolated from rat stomach using pronase digestion followed by repeated counter-flow elutriation and cultured for 48 h before secretion experiments. The release of histamine and pancreastatin was determined by radioimmunoassay. 3. None of the PGs tested stimulated the release of either histamine or pancreastatin. 4. PGE1 and PGE2 inhibited both gastrin- and PACAP-evoked histamine and pancreastatin secretion (IC50 = 1-2 x 10(-10) M). Most other naturally occuring prostanoids and PG congeners had no or little inhibitory effect. The PGE analogues misoprostol and sulprostone were more potent (IC50 = 0.9 x 10(-11) M and 2 x 10(-11) M respectively) than PGE1 and PGE2. The rank order of potency was misoprostol > sulprostone > PGE1 = PGE2, suggesting the involvement of the so-called EP3 receptor. 5. The effects of PGs on the stomach ECL cells may be direct or indirect, for instance through the stimulated release of somatostatin from contaminating D cells (2-3%). However, the amount of somatostatin in the cell culture after 48 h was below the limit of detection, and somatostatin immunoneutralization did not prevent misoprostol from inhibiting secretion from the ECL cells. 6. The misoprostol-induced inhibition was reversed by pertussis toxin suggesting the involvement of G-protein subunits G alpha(0) and/or G alpha(i). 7. In view of the potency by which PGE1, PGE2, misoprostol and sulprostone inhibited the stimulated release of histamine and pancreastatin, we suggest that the ECL cells represent a primary target for prostaglandins acting via an EP3 receptor in the oxyntic mucosa. 8. The results suggest that the clinically useful effect of misoprostol as an anti-ulcer drug reflects its ability to inhibit stomach ECL-cell histamine secretion.

PACAP stimulates gastric acid secretion during somatostatin immunoneutralization in rats

PACAP stimulates gastric acid secretion during somatostatin immunoneutralization in rats

Effects of calcitonin gene-related peptide on somatostatin and gastrin gene expression in rat antrum

The ability of exogenous calcitonin gene-related peptide (CGRP) to regulate gastric somatostatin and gastrin messenger RNA was studied in vitro in rat antral mucosal/submucosal tissues. Somatostatin and gastrin mRNA were quantified by Northern and dot blot hybridization and regulatory peptides were measured by radioimmunoassay. Incubation of antral tissues in the presence of CGRP (1×10 −7 M) for 60 min resulted in a reciprocal increase in somatostatin and a decrease in gastrin release: 214.7±28.5 vs. control of 81.7±5.9 pg somatostatin per gram of tissue and 2.2±0.3 vs. control of 5.5±0.7 ng gastrin per gram of tissue ( P<0.001). CGRP caused parallel changes in somatostatin and gastrin mRNA levels: somatostatin mRNA increased by 212% from 0.40±0.02 to 1.25±0.09 absorbance units (AU) ( P<0.001) and gastrin mRNA decreased by 73% from 0.55±0.08 to 0.15±0.02 AU ( P<0.001). Somatostatin monoclonal antibody prevented CGRP-mediated inhibition of both gastrin release and gastrin mRNA levels. In conclusion, CGRP is capable of modulating both the secretion and gene expression of regulatory peptides from antral G and D cells. Somatostatin immunoneutralization studies suggest that the actions of CGRP on gastrin release and gene expression are indirect and mediated through the paracrine influences of somatostatin.

Effect of somatostatin immunoneutralization on gastric acid and pancreatic enzyme secretion in anesthetized rats

The involvement of somatostatin in urethane-anesthesia-evoked suppression of gastric acid secretion has been described. The present study has examined the role of endogenous somatostatin in diminished pancreatic enzyme secretion during anesthesia, while monitoring acid secretion concurrently. Rats were anesthetized with either urethane or sodium pentobarbital. An indwelling catheter was placed into the right jugular vein. The esophagus and the pylorus were ligated, and the stomach was perfused with saline. The common bile duct was ligated at the hepatic hilum, and cannulated at the duodenal end of the duct for collecting pure pancreatic juice. Purified somatostatin monoclonal antibody (CURE.S6) or control antibody (keyhole limpet hemacyanin, KLH) was injected iv in increasing doses (0.05; 0.15; 0.5; and 1.5 mg) every 30 min ( n = 6). Gastric acid and pancreatic amylase secretions were measured. The effect of the antibodies on CCK-8-stimulated (0.25–2.50 nmol/kg/h) pancreatic amylase secretion was also tested. During urethane anesthesia somatostatin antibody induced a dose-dependent increase in acid output, while control antibody did not change it. Basal pancreatic amylase secretion was not affected by either somatostatin or by control antibody. Pancreatic secretory responses to high but not to low doses CCK-8 were found to be significantly increased following immunoneutralization of somatostatin. In sodium pentobarbital-anesthetized rats somatostatin antibody stimulated basal acid secretion but did not affect basal pancreatic amylase secretion. Our data indicate that in anesthetized rats endogenous somatostatin mediates suppression of basal gastric acid secretion but not that of basal pancreatic amylase secretion, and this action does not depend on the type of anesthesia. Furthermore, endogenous somatostatin may play a physiological role in modulating stimulated pancreatic enzyme secretion in this species.

The effect of immunization against somatostatin and β-agonist administration alone and in combination on growth and carcass composition in young steers

AbstractThe effect of active immunization against somatostatin and β-agonist administration alone and in combination on growth, carcass composition and endocrine responses was investigated in young steers given a pelleted diet of dried grass and barley (0·7: 0·3) ad libitum for 16 weeks. Immunization alone increased growth rate by proportionately 0·10 but had no effect on plasma growth hormone (GH) or insulin-like growth factor-1 (IGF-1) concentrations (P &gt; 0·10). Carcass protein content was unchanged but fat content tended to be increased. This was possibly associated with increased (P &lt; 0·10) plasma insulin concentrations observed in these animals. Cimaterol administration significantly increased growth rate (P &lt; 0·05) and carcass weight (P &lt; 0·01). Carcass protein content was significantly (P &lt; 0·01) increased and carcass fat was significantly (P &lt; 0·001) reduced. Administration of cimaterol to immunized animals resulted in an enhancement of the repartitioning effect of the pagonist although growth rates were intermediate between the separate treatments. The mechanism by which this was achieved is unclear. Plasma IGF-1 concentrations tended (P &lt; 0·10) to be lower in these animals compared with controls. Plasma insulin concentrations were also reduced (P &lt; 0·05) in these animals. Both immunized animals and those given cimaterol alone showed an increased GH response to a single intravenous injection of growth hormone releasing factor (GRF) (P &lt; 0·05). Animals given the combined treatment however showed a reduced response suggesting that the effects were not mediated through direct changes in GH secretion. The improved lean:fat ratio in the carcass was observed to be mediated through an enhancement of the lipolytic response to the /J-agonist with only small effects on protein accretion. It is suggested that immunoneutralization of somatostatin may increase the sensitivity of adipose tissue to lipolytic stimuli. This could occur through changes in the secretion of gastrointestinal or pancreatic hormones as a result of neutralization of the inhibitory influences of somatostatin. Further work is required to clarify these effects.

Tachykinins mediate vagal inhibition of gastrin secretion in pigs

BACKGROUND & AIMS: Electrical vagal stimulation activates both stimulatory and inhibitory nerve fibers regulating gastrin release in the porcine antrum. The aim of this study was to examine the role of tachykinins in the inhibitory vagal control of gastrin release in the porcine antrum. METHODS: Tachykinin presence was examined by immunohistochemistry and specific radioimmunoassays. Effects of electrical vagus stimulation and capsaicin infusion on tachykinin, gastrin, and somatostatin release were studied using the isolated perfused porcine antrum with intact vagal innervation. Effects of substance P and neurokinin A on gastrin and somatostatin secretion were investigated using nonpeptide neurokinin 1 and 2 receptor antagonists and somatostatin immunoneutralization. RESULTS: Porcine antrum contained substance P and neurokinin A and did not contain neurokinin B, with immunoreactive nerves situated close to gastrin- and somatostatin-immunoreactive cells. Vagus stimulation released substance P, neurokinin A, gastrin, and somatostatin, whereas capsaicin stimulated only tachykinin release Tachykinin infusions increased somatostatin and decreased gastrin secretion, the latter being unaffected by somatostatin immunoneutralization and both being blocked by a combination of neurokinin 1 and 2 receptor antagonists, which also increased gastrin output during vagal stimulation. CONCLUSIONS: Tachykinins strongly inhibit gastrin and stimulate somatostatin secretion in porcine antrum, and tachykininergic nerves mediate inhibitory vagal regulation of gastrin release. (Gastroenterology 1996 Oct;111(4):925-35)

Passive immunization against somatostatin increases resistance to Eimeria vermiformis infection in susceptible mice

The effect of in vivo immunoneutralization of somatostatin (SRIF) on Eimeria vermiformis intestinal infection was studied in resistant (BALB/c), and susceptible (C57BL/6) mouse strains. An anti-SRIF monoclonal antibody (MAb-SRIF) was used to passively immunize the mice by intraperitoneal injection. The animals were subsequently orally infected with oocysts of E. vermiformis. Individual fecal samples were collected daily for 21 days to monitor the kinetics of oocyst shedding. The fecal oocyst shedding was significantly higher in the C57BL/6 strain than in the BALB/c strain ( P < 0.01). Passive immunization with MAb-SRIF in the C57BL/6 mice significantly reduced the number of oocysts in feces ( P < 0.05), when compared to the infected non-immunized mice of the same strain. Infected BALB/c mice showed no difference in oocyst shedding in response to the passive immunoneutralization with MAb-SRIF. In conclusion, passive immunization with MAb-SRIF increased resistance to E. vermiformis infection in the susceptible C57BL/6 mice, but not in the resistant BALB/c mice. This suggests that SRIF modulates gut immune function in parasitic infection.

The potential of immuno-neutralization of somatostatin for improving pig performance

Abstract Immuno-neutralization of somatostatin (SRIF) has shown some promise as a technique for the enhancement of growth and lactation performance in sheep and cattle. In pigs, active immunization against SRIF has failed to promote growth. While a more consistent GH response to GRF injections in SRIF-immunized pigs has been described, the effects of this approach on mean plasma GH, IGF-I and thyroxine levels are equivocal. Since reproductive functions in the pig are affected by GH as well and since the existence of SRIF-like immunoreactivity has been proven in porcine ovaries, the influence of immuno-neutralization of SRIF on reproductive performance has also been investigated. In one report ovulation rates and first litter size tended to be higher, while own work only describes adverse effects on ovarian activity. Although passive transfer of immunity against SRIF through colostrum to litters has been shown, preweaning survival and mean pig weaning weight were not improved. In conclusion, so far there is no indication to suggest that in the near future immuno-neutralization of SRIF might become a practical tool to improve pig performance, possibly because of the poor antibody response in pigs. In addition evidence exists in vivo and in vitro, that SRIF besides its well known negative effect, may also stimulate GH release providing another possible explanation why all attempts to improve pig performance through immuno-neutralization of SRIF have failed so far.

Effect of PACAP on gastric acid secretion in rats.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a new VIP-like brain-gut peptide. Its effects on the motility and secretory functions of the gastrointestinal system have been shown in previous studies. In this study we investigated the effect of intravenous PACAP on gastric acid secretion in conscious pylorus-ligated rats and in gastric fistula rats. PACAP showed significant inhibitory effects on pentagastrin- and histamine-stimulated gastric acid secretion, but no effect on basal or carbachol-stimulated secretion in pylorus-ligated rats. It did show dose-related inhibitory effects both on basal gastric acid secretion and on secretion stimulated by pentagastrin, histamine, or carbachol in gastric fistula rats. PACAP did not alter serum gastrin levels. Inhibition of prostaglandin synthesis with indomethacin and immunoneutralization of somatostatin with anti-somatostatin serum did not prevent the inhibitory effect of PACAP on gastric acid secretion in pylorus-ligated rats. We conclude that PACAP most likely has a direct effect on parietal cells and that this effect may be mediated, at least partially, by inhibition of the action of histamine on parietal cells.

Somatostatin antibody does not influence bombesin-induced inhibition of gastric acid secretion in rats

The influence of peripheral somatostatin immunoneutralization on intravenous (i.v.) and intracerebroventricular (ICV) bombesin-induced inhibition of gastric acid secretion (GAS) was investigated with the somatostatin monoclonal antibody, CURE.S6, in rats. The somatostatin antibody, injected i.v. in conscious rats with a chronic gastric fistula and i.v. catheter, did not modify basal GAS, whereas in urethane-anesthetized rats the basal GAS was increased by 150%. In conscious rats, somatostatin (15 micrograms/kg/h, i.v.) inhibited basal GAS by 50% after injection of control antibody but not after pretreatment with the somatostatin antibody. With pretreatment with a control antibody, bombesin (10 micrograms/kg/h, i.v.) inhibited basal GAS by 60% in conscious rats and by 50% the acid response to pentagastrin infusion in urethane-anesthetized rats. Bombesin injected ICV (3 and 10 ng/10 microliters/rat) inhibited basal GAS by 50% and 70%, respectively, in conscious rats pretreated with a control antibody. The somatostatin antibody injected i.v. before i.v. or ICV injection of bombesin did not influence bombesin-induced inhibition of GAS in conscious or anesthetized rats. These results show that peripheral somatostatin does not play a major role in the inhibition of gastric acid secretion induced either by ICV or i.v. administration of bombesin or basal acid secretion in conscious rats.

Immunomodulatory approaches for regulation of growth and body composition

AbstractHormonal growth promoters (growth hormone (GH), β-adrenergic agonists, steroids) which improve growth rate and/or lean: fat ratios in the carcass have received considerable adverse publicity and are either banned or have no licence for their use in countries of the European Community. This has led to the development of a number of techniques, involving the use of antibodies, aimed at regulating metabolic processes involved in determining growth and body composition.A number of these approaches have focused upon the GH axis, for example immunoneutralization of somatostatin (which normally inhibits GH secretion) to improve growth, the use of antibodies to GH which can enhance its effects in vivo and the development of antibodies which mimic the actions of GH. Although immunization against somatostatin has led to increased growth rates in a number of studies other studies have failed to demonstrate such an effect. A precise understanding of the mechanism of action of this approach is required before we can begin to understand why success is not assured. Antibodies which enhance GH action clearly do work reproducibly but the major problem in developing this approach is to produce an inexpensive peptide immunogen (its sequence derived from GH) which can be used to actively immunize animals so that their own antibodies enhance endogenous GH activity. Anti-idiotypic mimics of GH have also been produced which have GH actions in vivo but again this approach is of limited value until appropriate vaccines can be developed.A different approach to the problem of excess fat deposition involves the use of antibodies directed against the plasma membranes of adipocytes in order to elicit their destruction and thereby limit the storage capacity for fat. This technique has been demonstrated in rats, sheep and pigs in both passive and active immunization techniques. Once again, however, this promising approach is limited by the lack of a commercially suitable vaccine. The identification of individual membrane proteins which are antigenic has been achieved and this provides the prospect of producing recombinant DNA-derived vaccines.Whether these new approaches will be perceived as acceptable to the general public remains a serious concern and a potential limitation to their development as many would-be sponsors cut back their support for research in these areas.

Endogenous somatostatin inhibits histamine release from canine gastric mucosal cells in primary culture

The effects of somatostatin on histamine release were studied using primary cultures of canine oxyntic mucosal cells in which mast cell content was reduced by density gradient. The S6 monoclonal antibody to somatostatin, but not control antibodies, enhanced gastrin-stimulated histamine release. In the presence of S6, the somatostatin analogue SMS-201-995 (10(-7) M) inhibited gastrin-stimulated histamine release by 95%. The dose producing 50% inhibition for this inhibition was approximately 3 x 10(-10) M and was completely reversed by pertussis toxin treatment. In contrast to somatostatin, epinephrine failed to inhibit this gastrin stimulation. However, the lectin concanavalin A (ConA) also stimulated histamine release from these cultures, and this response was inhibited by epinephrine but not by somatostatin. Thus somatostatin selectively inhibited the gastrin-responsive histamine pool, which presumably is stored in oxyntic mucosal endocrine cells. In contrast, epinephrine selectively inhibits histamine release from the ConA-sensitive pool, which is presumably stored in mast cells. Furthermore, enhancement of gastrin-stimulated histamine release by immunoneutralization of somatostatin indicates an important role for endogenous somatostatin as a paracrine inhibitor of non-mast cell histamine release.