Effect of gut regulatory peptides on intestinal luminal fluid in the rat

The effect of intravenous gastrointestinal peptide hormone administration on net fluid transport in the small intestine was assessed in the rat. An increased fluid content was observed during vasoactive intestinal peptide, gastric] inhibitory peptide, and neurotensin infusions, and a decreased content with somatostatin, substance P and pancreatic polypeptide, by comparison with the control series. Motilin had no significant effect on luminal fluid volume. These results suggest that several of the gastrointestinal regulatory peptides may have an influence on the processes of fluid absorption and secretion by the small intestine.     

The effects of various peptides on the isolated pulmonary artery

Helical strips of pulmonary arteries from rabbits were tested for their responses to the following peptides: neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), cholecystokinin-octapeptide (CCK), somatostatin (SS), bombesin, neurotensin and gastrin. SP, in the absence of active base-tension, and NPY both induced concentration-dependent contractions, while VIP and SP, in the presence of active base-tone, and CCK induced relaxation. The pD2 (-log ED50) was in the order of NPY greater than SP and SP greater than CCK greater than VIP. SS, bombesin, NT and gastrin had no effect. These findings suggest peptidergic involvement in the vessels.     

Regulatory peptides in the gastrointestinal tract of Alligator mississipiensis

Summary The gastrointestinal tract of the alligator Alligator mississipiensis has been investigated for the presence of immunoreactivity to fourteen regulatory peptides all known to occur in the mammalian gut system.Mucosal endocrine cells reacting specifically with the antisera to neurotensin, C-terminal gastrin, somatostatin, bombesin, secretin, pancreatic glucagon and enteroglucagon were detectable, the distribution of these cells being, in general, similar to the mammalian pattern. Peripheral nerve cell bodies and nerve fibres were detected with the antisera to vasoactive intestinal polypeptide, substance P, bombesin and somatostatin again with a distribution similar to that seen in mammals.No immunoreactivity was observed with the available antisera to glicentin, motilin, gastric inhibitory polypeptide, gastrin 34, cholecystokinin 9–20 and met-enkephalin.     

Somatostatin inhibits bombesin-induced effects on migrating myoelectric complexes in the small intestine of the rat

The effect of i.v. infusions of bombesin and somatostatin, administered either separately or in combination, on migrating myoelectric complexes (MMCs) in the small intestine were studied in conscious, fasted rats. The myoelectrical activity was recorded by means of three bipolar electrodes chronically implanted into the duodenum and jejunum. Infusion of bombesin (0.5, 0.9 and 3 pmol . kg-1 . min-1) interrupted the MMC and induced irregular spiking activity similar to that observed on feeding. Only after the highest dose a consistent inhibition of the MMCs and a significant increase (P less than 0.05) of the spiking activity were achieved at all recording levels. Somatostatin (90 pmol . kg-1 . min-1) did not interrupt the MMC, but reduced significantly the incidence of the activity fronts and spiking activity of the MMCs (P less than 0.05). The effects of bombesin (3 pmol . kg-1 . min-1) on the MMC pattern were inhibited by simultaneous infusion of somatostatin (P less than 0.05). In a second series of experiments, using anesthetized rats, infusion of bombesin (0.5 and 3 pmol . kg-1 . min-1) increased the plasma concentration of neurotensin- gastrin-like immunoreactivities in a dose-dependent manner. The results show that bombesin alters the myoelectrical activity of the small intestine from a fasting to a fed pattern. Since the effect of bombesin was inhibited by the hormone release inhibitor somatostatin, it is suggested that the effect of bombesin on MMC may be secondary to the release of gastrointestinal peptides, such as neurotensin or gastrin.     

Imagerie phénotypique et peptides radiomarqués au gallium-68 : au-delà des analogues de la somatostatine

Receptor targeting with radiolabeled peptides has become very important in nuclear oncology in the past few years. The most frequently used peptides in the clinic are analogs of somatostatin. However, other radiolabeled analogs have also been developed and assessed in vitro and in vivo and some of them are already in clinical use. For instance, radiolabeled analogs of alpha-melanocyte-stimulating hormone (alpha-MSH), neurotensin, vasoactive intestinal peptide (VIP), bombesin (BN), substance P (SP), cholecystokinin (CCK), integrins… This review focuses on gallium-68 radiolabeled peptides developed for PET imaging, except for somatostatin analogs, which are discussed in another article.     

The presence of immunoreactive vertebrate bioactive peptide substances in hemocytes of the freshwater snailViviparus ater (gastropoda,prosobranchia)

1. Using an immunocytochemical procedure a wide range of immunoreactive vertebrate bioactive peptides (BAPs) has been found in hemocytes of Viviparus ater: bombesin, calcitonin, CCK-8, CCK-39, GH, glucagon, insulin, oxytocin, neurotensin, secretin, serotonin, somatostatin, substance P, vasopressin, and VIP. 2. No immunostaining was observed for antigastrin and antithyroglobulin antibodies. 3. The presence of BAP-like molecules in hemocytes suggests a correlation between hemocyte and APUD cells and is evidence of a relationship between the neuroendocrine and the immune systems.     

Actions of various gastrointestinal peptides on the isolated amphibian spinal cord.

The effects of a number of peptides which are found in the gastrointestinal tract have been ascertained on the direct current recorded dorsal and ventral root responses of the isolated hemisected toad spinal cord. Motilin, substance P, bombesin, neurotensin, and thyrotropin releasing hormone had potent depolarizing actions on dorsal root terminals and motoneurons. These substances evoked discernable effects at concentrations as low as 10--7 M, or even lower with motilin. The effects of motilin, neurotensin, and thyrotropin-releasing hormone were greatly reduced or abolished by perfusion of the preparation with tetrodotoxin. Adrenocorticotrophic hormone, secretin, and pancreozymin (cholecystokinin) also depolarized dorsal root terminals and motoneurons. The effects of secretin and cholecystokinin were not abolished by tetrodotoxin. Leu- and Met-enkephalin had weak hyperpolarizing actions on the dorsal and ventral root potentials of repetitively stimulated preparations. Gastrin, gastric inhibitory peptide, glucagon, and somatostatin had no apparent effects on the responses of the preparation. Angiotensin and vasopressin both had rather weak depolarizing effects on the dorsal and ventral roots.     

Neuropeptides and thermoregulation: the interactions of bombesin, neurotensin, TRH, somatostatin, naloxone and prostaglandins

In this study we have examined the interactions of bombesin (1 microgram ICV), neurotensin (1 microgram ICV), TRH (10 micrograms ICV), somatostatin (10 micrograms ICV), PGE2 (10 micrograms ICV) and naloxone (10 mg/kg SC) on thermoregulation in the rat at room temperature (20 +/- 1 degree C). Given alone, bombesin, neurotensin, somatostatin and naloxone all produced hypothermia (bombesin greater than neurotensin greater than somatostatin congruent to naloxone). PGE2 was hyperthermic, and TRH had no effect. Bombesin and PGE2 neutralized one another's effects. Neurotensin had no effect on PGE2-induced hyperthermia. Naloxone enhanced the hypothermic effect of bombesin and somatostatin enhanced the rate of onset of hypothermia after bombesin. TRH had no effect on bombesin-induced hypothermia. TRH, somatostatin and naloxone had no effect on neurotensin-induced hypothermia. TRH antagonized the hypothermia due to naloxone and somatostatin.     

Morphine addiction and withdrawal alters brain peptide concentrations

This study demonstrates that, during morphine addiction and withdrawal in rats profound alterations in the concentrations of a variety of brain peptides occur. Somatostatin, cholecystokinin, neurotensin and substance P concentrations increased during morphine addiction. Naloxone-induced withdrawal decreased brain concentrations of TRH, somatostatin, neurotensin and substance P. Naloxone alone decreased thalamic substance P and neurotensin concentrations. Vasoactive intestinal peptide concentrations were unaltered by any of the treatments. The fall in the tissue concentration of somatostatin during naloxone-induced withdrawal correlated well with the fall in the circulating growth hormone, suggesting that this could be secondary to somatostatin release. Our data support the hypothesis that brain peptides, acting locally in the brain as neuromodulators, play an important role in the genesis of the syndromes of morphine addiction and withdrawal.     

Mast cell heterogeneity: effects of neuroenteric peptides on histamine release

Recent reports suggesting that the actions of certain neuroenteric peptides may be mediated in part by the secretion of histamine and other mast cell contents could have important implications for gastrointestinal motility and secretion. However, evidence for a mast cell-hormonal interaction is based on studies using peritoneal or cutaneous mast cells. Because intestinal mucosal mast cells (MMC) differ functionally from peritoneal mast cells (PMC), we compared the effects of several neurotransmitters and intestinal hormones on histamine secretion from two mast cell types in the rat. MMC hyperplasia was induced in rats by infection with the nematode Nippostrongylus brasiliensis, and MMC were isolated from the small intestine by collagenase digestion. Substance P, somatostatin, vasoactive intestinal polypeptide (VIP), neurotensin, and bradykinin had a potent secretagogue effect on (10(-7) to 10(-4)M) PMC which was temperature-, energy-, and calcium-dependent. In contrast to PMC, MMC released significant amounts of histamine only when challenged with substance P. Acetylcholine, bombesin, motilin, and pentagastrin had no secretory effect on either PMC or MMC. The differences between PMC and MMC in responsiveness to peptides could not be attributed to the MMC isolation procedure because PMC treated similarly or mixed with MMC suspensions retained their responsiveness to these stimuli. Our results extend the concept of neurocrine control of mast cell function, but indicate that mast cells from different sites have distinct profiles of responsiveness to regulatory peptides.     

Intrathecal substance P and somatostatin in rats: behaviors indicative of sensation

Biochemical, histochemical and neurophysiological data suggest that substance P and somatostatin are neurotransmitters for primary afferent neurons. This study used intrathecal administration of these peptides and others (neurotensin and vasoactive intestinal polypeptide) in chronically catheterized, environmentally adapted, freely moving rats to evaluate their effects on unconditioned behavior. Substance P and somatostatin each elicited behaviors which were dose related. The behaviors included caudally directed biting and licking along with hindlimb scratching, writhing and retching. The behavioral responses were rapid in onset (1 min) and, in the case of substance P, short in duration (3 min). Vehicle, neurotensin and vasoactive intestinal polypeptide were without effect. These results demonstrate the ability of substance P and somatostatin to induce behavior in rats upon intrathecal administration and extend previous studies in mice.     

Molecular forms of somatostatin, substance P and neurotensin in fresh human cerebral cortex

The molecular forms of somatostatin, substance P and neurotensin in fresh normal human cerebral cortex have been investigated using high performance liquid chromatography and radioimmunoassay. For each peptide most of the immunoreactivity measured corresponds to a single molecular form co-eluting with the authentic peptide. Small differences in the minor peaks of somatostatin and substance P immunoreactivity are seen when compared to the results of similar studies on post mortem human brain. A substantial difference in the molecular forms of neurotensin was seen which suggests that degradation of this peptide may occur post mortem.     

Neuroendocrine peptide levels in the gastrointestinal tract of mice after unilateral cervical vagotomy

The effects of left and right unilateral cervical vagotomy on the content of several neuroendocrine peptides were studied in different parts of the murine gastrointestinal tract, known to receive vagal innervation. The neuroendocrine peptides investigated were secretin, gastric inhibitory peptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, substance P, VIP, neurotensin, neuropeptide Y (NPY), and galanin. The neuroendocrine peptide concentration was affected after both left and right vagotomy, and that the changes in the concentrations of the neuroendocrine peptide levels occurred in all the gastrointestinal segments investigated, namely antrum, small and large intestine. However, these changes varied, depending on which side was vagotomized and the interval after vagotomy. It is concluded that the vagus nerve had an important impact on the neuroendocrine system in the murine gut. It is suggested, furthermore that the contradictory results obtained earlier on the effect of vagotomy on the gastrointestinal peptides may depend on differences in the vagotomy methods used and on differences in observation time after vagotomy.     

Neurotransmitters in the intestine of the Atlantic cod, Gadus morhua

The effects of the putative neurotransmitters acetylcholine, adrenaline, adenosine, ATP, bombesin, 5-hydroxytryptamine, met-enkephalin, neurotensin, somatostatin, substance P and VIP have been investigated in the perfused intestine of the cod, Gadus morhua. The presence and distribution of the different types of nerves was investigated with immunohistochemistry and Falck-Hillarp fluorescence histochemistry. A spontaneous rhythmic activity of the perfused preparations usually occurred within a few minutes from the start of the experiment. This activity was diminished or abolished by addition of atropine, methysergide or tetrodotoxin to the perfusion fluid. Acetylcholine, 5-hydroxytryptamine or substance P caused a contraction of the intestinal wall. The response to acetylcholine was blocked by atropine but not by tetrodotoxin, while the response to 5-hydroxytryptamine was blocked by methysergide and usually also by tetrodotoxin. This indicates that the effect of acetylcholine is direct on the muscle cells, while the effect of 5-hydroxytryptamine may be at least partly via a second neuron. All adrenergic agonists (adrenaline, isoprenaline and phenylephrine) had a dominating inhibitory effect on the intestine. Experiments with antagonists showed that the inhibition is due to stimulation of both alpha-adrenoceptors and beta-adrenoceptors. ATP, adenosine and somatostatin also caused a relaxation of the intestinal wall, often followed by a contraction. Met-enkephalin produced variable responses, either a relaxation, a contraction or both. Bombesin caused a weak inhibition, if anything. Neurotensin and VIP did not visibly affect the intestinal motility. 5-HT-, substance P- and VIP-like immunoreactivity and catecholamine fluorescence were observed in the myenteric plexus, submucosa and muscle layers in all parts of the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical evidence of gastro-entero-pancreatic neurohormonal peptides of vertebrate type in the nervous system of the larva of a dipteran insect, the hoverfly, Eristalis aeneus

Using rabbit and guinea-pig antisera, raised against GEP neurohormonal peptides of mammalian origin, cells were observed in the brain and/or in the fused ventral ganglia of the last (fifth) larval instar of the hoverfly, Eristalis aeneus, being immunoreactive with antisera against insulin, somatostatin, glucagon, PP, secretin, gastrin/CCK/caerulein; substance P, enkephalin and endorphin. Most of these GEP neurohormonal peptides also occurred in nerve fibers. No immunoreactive cells or nerve fibers could be detected with antisera against GIP, VIP, (the central fragments of) CCK, bombesin or neurotensin. The antisera tested failed to reveal any immunoreactive cells or nerves in Weismann's ring (fused corpus allatum/corpus cardiacum and thoracic gland) or in different parts of the alimentary tract. The observations support the hypothesis that neuronal GEP hormonal peptide production in the brain is a genuinely original mechanism and the appearance of endocrine cells in the gut a later feature in evolution.     

Neuropeptides in the gastrointestinal canal of Necturus maculosus

Summary The presence and distribution of regulatory peptides in nerves and endocrine cells of the stomach, intestine and rectum of a urodele amphibian, the mudpuppy, Necturus maculosus, was studied immunohistochemically in sections or whole-mount preparations of the gut wall. The effect of the occurring peptides on gut motility was studied in isolated strip preparations of circular and longitudinal smooth muscle from different parts of the gut.Bombesin-, neurotensin-, substance P- and VIP-like immunoreactivity was present in abundant nerve fibres in the myenteric plexus of both stomach, intestine and rectum. Single fibres or bundles were present in the circular muscle layer and in a well-developed deep muscular plexus in the intestine and rectum. Immunoreactive nerve cells were found in the myenteric plexus of the stomach, intestine (neurotensin only) and rectum. Gastrin/CCK-like immunoreactivity was observed only in a few fibres in stomach and rectum.Endocrine cells containing bombesin-, met-enkephalin-, gastrin/CCK-, neurotensin-, somatostatin- or substance P- like immunoreactivity were present in the mucosa.The effect of bombesin was an inhibition of the rhythmic activity in circular muscle preparations and in longitudinal muscle from the rectum, while longitudinal muscle from the stomach usually responded with a weak increase in tonus. Neurotensin, like bombesin, was inhibitory on the spontaneous rhythmic activity of circular muscle throughout the gut, while the effect on longitudinal muscle was an increase in tonus. Met-enkephalin and substance P increased the tonus of all types of preparations, and often, in addition, initiated a rhythmic activity superimposed on this maintained tonus. VIP had a general inhibitory effect on the preparations, decreasing tonus and/or abolishing rhythmic activity.It is concluded that bombesin-, neurotensin-, substance P- and VIP-like peptides are present in nerves throughout the urodele gut and may have physiological functions in regulating the motility of the gut. The gastrin/CCK-like peptide present in nerves of the stomach and rectum may affect the function of these parts of the gut. The regulatory peptides present in endocrine cells may, perhaps with the exception of the somatostatin-like peptide, affect the motility humorally.     

The effect of some brain/gut peptides on plasma cholesterol levels in the rat

The effect of substance P (SP), bombesin (BBS), somatostatin (SRIF) and neurotensin (NT) on the plasma cholesterol levels was studied in the rat. SP and BBS had no effect, but SRIF produced a significant transient hypocholesterolemia and NT a significant transient hypercholesterolemia 15 minutes after the intravenous injections. Neither SRIF nor NT influenced the rate of the 7-hydroxylation of cholesterol. The data suggest a relation of SRIF and NT to the maintenance of the plasma cholesterol concentration.     

Reduced hypothalamic somatostatin and neuropeptide Y concentrations in the spontaneously-diabetic Chinese hamster

Hypothalamic concentrations of six regulatory peptides having central effects on appetite and/or glucoregulation were measured by radioimmunoassay in spontaneously-diabetic Chinese hamsters and in age- and sex-matched non-diabetic control animals. In the diabetic hamsters, hypothalamic concentrations of somatostatin and neuropeptide Y were significantly reduced by 25-30% below controls. None of the other four peptides examined (bombesin, galanin, neurotensin and vasoactive intestinal peptide) differed significantly between the two groups. Disturbances in neuropeptide Y (the most potent central appetite stimulant yet discovered) and in somatostatin could be related to hyperphagia, an early and possibly primary abnormality of the diabetic syndrome in the Chinese hamster.     

The effect of some brain/gut peptides on plasma cholesterol levels in the rat

The effect of substance P (SP), bombesin (BBS), somatostatin (SRIF) and neurotensin (NT) on the plasma cholesterol levels was studied in the rat. SP and BBS had no effect, but SRIF produced a significant transient hypocholesterolemia and NT a significant transient hypercholesterolemia 15 minutes after the intravenous injections. Neither SRIF nor NT influenced the rate of the 7α-hydroxylation of cholesterol. The data suggest a relation of SRIF and NT to the maintenance of the plasma cholesterol concentration.     

Prevention by bombesin of cold-restraint stress induced hemorrhagic lesions in rats

Several neuropeptides, injected intraventricularly (ivt), were assessed for their effects on cold-restraint-induced hypothermia and hemorrhagic gastric lesions in 24 hr fasted rats. Bombesin (5-1 μg) further enhanced the drop in body temperature following stress and markedly prevented the gastric erosions in a dose-dependent fashion (5-0.1 μg). β-endorphin exerted a similar effect, but only at the 5 μg dose level. Other peptides (neurotensin, substance P, somatostatin and TRH: 5 μg) did not influence susceptibility to the gastric mucosal damage. Somatostatin and TRH reduced the hypothermic effect of stress. Bombesin is 250 times less potent when injected systemically than ivt and its actions are not reversed by nalaxone. The prevention of gastric erosions by bombesin could initially involve a central mechanism of action, independent of opiate receptors and possibly related to the sustained and marked hyperglycemia observed in bombesin treated rats exposed to stress.