Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of the genetic defects which define the obese (ob) and diabetes (db) loci in mice remain unknown, but both produce similar syndromes when maintained in the same strain of mice. There is some evidence suggesting a lesion in the central nervous system (CNS) in db/db mice, while ob/ob mice appear to have a primary lesion outside the CNS. In a search for further evidence of a unique central lesion in db/db mice, we have examined neuropeptide content in selected, microdissected brain areas in both of these mutants and lean controls. In order to rule out possible interactions of the db mutation with the genetic background, diabetes mice of both C57BL/KsJ and C57BL/6J strains were studied. When concentrations of nine neuropeptide immunoreactivities were examined in up to seven microdissected areas of the brain, C57BL/6J ob/ob mice showed only one reproducible alteration, a lower content of beta-endorphin-like immunoreactivity (LI) in the preoptic area at both 3 and 6 weeks of age as compared with lean littermates. In contrast, db/db mice of both C57BL/6J and C57BL/KsJ strains exhibited alterations in a total of four peptides in three brain areas: lower concentration of somatostatin-LI in median eminence, higher Met-enkephalin-LI in dorsal vagal complex of the medulla oblongata, higher substance P-LI and lower vasoactive intestinal polypeptide (VIP)-LI in amygdala. The concentrations of the peptides studied in medial basal hypothalamus, lateral hypothalamus, substantia nigra, and preoptic area were not reproducibly altered in db/db mice. These data provide preliminary evidence for unique brain abnormalities in db/db mice in specific areas that are involved in processing of neural signals that can affect the islets of Langerhans, gonadotrophin secretory patterns, and many other visceral functions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Unique alterations of neuropeptide content in median eminence, amygdala, and dorsal vagal complex of 3- and 6-week-old diabetes mutant mice. 223 77

Partially purified nerve varicosities prepared from canine small intestinal myenteric, deep muscular and submucosal plexuses were found to contain, by radioimmunoassay, gastrin-releasing polypeptide (GRP), substance P, Leu-enkephalin, Met-enkephalin, vasoactive intestinal polypeptide (VIP) and neurokinin A, but did not contain detectable amounts of neurokinin B. In all three plexus preparations, VIP was present in the highest concentration. In contrast to other species, GRP and the enkephalins were found to be present in relatively high concentrations in the submucosal plexus and GRP was present in low concentrations in the deep muscular plexus. Equal concentrations of substance P and neurokinin A were found in the myenteric and deep muscular plexus preparations but greater concentrations of substance P relative to neurokinin A were found in the submucosal plexus preparations. On reverse phase HPLC, a major peak of immunoreactivity occurred at the retention times of standard preparations for all six neuropeptides measured. Significant heterogeneity was found for GRP- and VIP-like immunoreactivity, especially in the submucosal plexus preparations. These partially purified canine small intestine nerve varicosity preparations may prove of value in studying release mechanisms for, and the posttranslational processing of, neuropeptides.
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PMID:Canine myenteric, deep muscular, and submucosal plexus preparations of purified nerve varicosities: content and chromatographic forms of certain neuropeptides. 234 94

In 15 dogs, cobalt chloride solutions were infused close intra-arterially to perfuse a short segment of the jejunum. In an additional four dogs, the jejunum was perfused with the aqueous vehicle (perfusion control). All animals were killed after 1 mo and tissue samples from cobalt-treated and from nonperfused intestine (tissue comparison control) were obtained for electron microscopic and immunohistochemical studies. Segments infused with 0.25 g/dl cobalt solution showed minimal changes; the most striking feature was an increase of vasoactive intestinal polypeptide (VIP)- and substance P-containing neurosecretory granules. Cobalt chloride at higher concentrations (0.75-1.5 g/dl) induced degeneration of ganglion cells and axons in both the myenteric and submucosal plexi. In contrast, the smooth muscle and the mucosal cells of the cobalt-perfused intestine showed no histological abnormalities. Immunohistochemical staining of tissues treated with 0.75-1.5 g/dl cobalt solutions revealed absence of substance P, Met-enkephalin, and VIP immunoreactivity in all section studied; control segments showed the presence of all three peptides. Cobalt chloride in concentrations of 0.75-1.5 g/dl causes degeneration of intestinal intramural nerves and provides an experimental model suitable for studying the role of these nerves in small intestinal function.
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PMID:Chemical degeneration of intestinal nerves. 236 Jun 31

The effects of opioids and naloxone on cyclical forestomach motility were determined in anaesthetized and conscious sheep. To assess central or peripheral opioid actions, differential routes of administration were used. Possible dynamic effects along the innervating vagovagal reflex arc were investigated electrophysiologically at the cervical level of the vagus nerve. Further, direct influences on the smooth muscle were evaluated in vitro on isolated longitudinal reticular strips. Additionally, the effects of some spasmogenic agents were studied for comparative purposes. In anaesthetized sheep, opioids depressed in an identical manner both the amplitude of spontaneous cyclical contractions and contractions evoked by electrical stimulation of the distal end of the cut cervical vagus. In conscious sheep, low doses of normorphine and loperamide inhibited frequency and amplitude centrally (20 micrograms/kg and 4 micrograms/kg via carotid artery respectively), whereas locally higher dose levels (200 micrograms/kg and 10 micrograms/kg via coeliac artery respectively) affected only the amplitude of cyclical contractions. Furthermore the opioid peptides Leu-, Met-enkephalin and [D-Ala2-Met5]-enkephalinamide preferentially depressed the amplitude of cyclical motility most efficiently if administrated via the coeliac artery. These results indicate the presence both of a central opioid action depressing frequency and amplitude and of a local opioid action depressing only the amplitude of cyclical reticulo-ruminal motility. Opioids did not alter the resting discharge of afferent tension units and similarly failed to modulate tone of reticular strips in vitro, suggesting that the opioids act locally on the intramural neuronal plexus, possibly by diminishing the output of excitatory transmitter. Whether substance P could play a role as a vagal excitatory transmitter besides the classically implicated acetylcholine has been discussed. The central opioid mechanism is probably not situated within the gastric centres but elsewhere in the brain. Naloxone (greater than or equal to 100 micrograms/kg, jugular vein) stimulated the frequency of cyclical ruminal motility only in well-defined experimental conditions, probably via a central mechanism.
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PMID:Central and local actions of opioids upon reticulo-ruminal motility in sheep. 240 75

As part of a series of studies in which we are attempting to determine the roles of the lateral spinal (LSn) and lateral cervical (LCn) nuclei in somatic sensation, we have examined the fibers and terminals within these nuclei in the rat using the indirect immunofluorescence technique. Eleven antisera were used. Within the LSn, antisera against dynorphin 1-8 (DYN), substance P (SP), and Met-enkephalin (ENK) produced labeling of a large number of processes in all segmental levels examined. Processes labeled with these antisera frequently apposed the cell bodies and dendrites of LSn neurons. Antisera against somatostatin (SOM) and FMRF-NH2 (FMRF) labeled smaller numbers of processes within the LSn. Few, if any, processes in the LSn were labeled using antisera against serotonin, cholecystokinin octapeptide, oxytocin, neurotensin, corticotrophin-releasing factor, and vasoactive intestinal polypeptide. In contrast to the LSn, the LCn contained virtually no labeled processes irrespective of the antiserum employed. An area was found adjacent to the LCn in the medial portion of the dorsal lateral funiculus (DLf) of C2 that resembled the LSn in several of its anatomical characteristics: like the LSn, the medial portion of the C2 DLf contained small multipolar neurons; it was similar to the LSn in its medial-lateral extent; and following staining with each antiserum, the LSn and the medial DLf of C2 contained a similar number of labeled processes. The peptide-containing area in the medial DLf of C2 was found to be continuous with the LSn. We therefore propose that this region is a rostral extension of the LSn.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical studies of the peptidergic content of fibers and terminals within the lateral spinal and lateral cervical nuclei. 241 May 76

The occurrence and distribution of substance P (SP)-like, methionine-(Met)- and leucine-(Leu)-enkephalin-like, and FMRFamide-like immunoreactivities were determined in the neuroendocrine complex of the eyestalk of the fiddler crab, Uca pugilator, by immunocytochemistry. SP-like immunoreactivity was found in the optic peduncle, sinus gland, medulla externa, medulla interna, lamina ganglionaris, and retinular cells. Met-enkephalin-like and Leu-enkephalin-like immunoreactivity was observed in most of the retinular cells, optic peduncle, sinus gland, medulla terminalis, and lamina ganglionaris. However, Met-enkephalin-like, but no Leu-enkephalin-like, immunoreactivity was seen in the medulla terminalis X-organ. FMRFamide-like immunoreactivity could be seen in all parts of the eyestalk except in the sinus gland, lamina ganglionaris, and retinular cells. FMRF-amide-like activity was especially strong in the three chiasmatic regions connecting the optic ganglia. The possibility that these four peptides may function as neuroregulators in the fiddler crab is discussed.
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PMID:Localization of substance P-like, leucine-enkephalin-like, methionine-enkephalin-like, and FMRFamide-like immunoreactivity in the eyestalk of the fiddler crab, Uca pugilator. 241 11

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.
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PMID:Neuropeptides in the gastrointestinal canal of Necturus maculosus. Distribution and effects on motility. 241 14

The substance P and Met-enkephalin content were measured in the rat lumbar spinal cord after monolateral section of the sciatic nerve. The proximal stump of the lesioned nerve was either ligated, limiting the formation of neuroma, or sutured intraperitoneally, allowing the formation of a very large neuroma. Both types of lesion caused a similar peptide loss. Substance P and Met-enkephalin decreased by about 50% 10 days following the lesion. Such a loss was maintained even 30 days postoperatively and was not affected by the neuroma size. Immunohistochemical stainings showed that the loss of both peptides occurred in laminae I and II of the dorsal horn. It is suggested that pain sensation developing after peripheral nerve lesion may be due to the intraspinal loss of enkephalin rather than to the neuroma formation.
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PMID:Peripheral nerve lesions cause simultaneous alterations of substance P and enkephalin levels in the spinal cord. 241 40

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)
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PMID:Neurotransmitters in the intestine of the Atlantic cod, Gadus morhua. 241 59

This study reports on a difference in the inhibitory action of the neuropeptides somatostatin and Met-enkephalin on acetylcholine (ACh) release from myenteric plexus-longitudinal muscle strips of guinea pig small intestine. Met-enkephalin (8.7 X 10(-8) M) inhibited ACh release evoked by either substance P (3.7 X 10(-8) M) or neurotensin (7.5 X 10(-11) M), and this inhibition could be reversed by naloxone (5 X 10(-8) to 5 X 10(-5) M). Neurotensin-induced ACh release was also sensitive to the inhibition by somatostatin. However, when tested in a dose range from 6.1 X 10(-8) to 6.1 X 10(-6) M, somatostatin was ineffective in reducing the efflux of ACh evoked by substance P. These observations provided evidence to support the view that inhibitory peptidergic neurons within the myenteric plexus modulate the activity of cholinergic neurons with a high degree of specificity and that both somatostatin and Met-enkephalin have distinct neuromodulatory functions in the gut.
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PMID:Inhibitory peptidergic neurons: functional difference between somatostatin and enkephalin in myenteric plexus. 241 98


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