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)

We sought to determine whether chronic guanethidine (Gu) treatment in adult rats produces depletion of sympathetic neurons and hyperinnervation by sensory neuropeptides in the celiac/superior mesenteric (C/SMG) ganglion. Rats received Gu 40 mg/kg per day i.p or saline for 5 weeks. Upon completion of treatment, the C/SMG and the superior cervical ganglion (SCG) were examined for neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP), both by immunocytochemistry (ICC) and radioimmunoassay (RIA). Gu produced marked depletion of NPY-containing neurons and NPY content in the C/SMG, similar to that in the SCG (-89 +/- 2 vs. -92 +/- 4%, respectively). SP and CGRP immunoreactivities were significantly higher in control C/SMG as compared with SCG; after Gu treatment, there was no significant increase in either SP or CGRP in the C/SMG, however, both increased in the SCG. In contrast, VIP levels were similar in the SCG and C/SMG in controls and increased in the C/SMG but not in the SCG after Gu treatment. Thus, in adult rats, the C/SMG is as susceptible as the SCG to Gu treatment; the different pattern of hyperinnervation by SP, CGRP and VIP of the C/SMG as compared with the SCG may reflect the different sources for these neuropeptides in prevertebral as compared with paravertebral ganglia.
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PMID:Different reinnervation patterns in the celiac/mesenteric and superior cervical ganglia following guanethidine sympathectomy in adult rats. 805 42

The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine (PHI), calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), galanin (GAL) and enkephalins (ENK) is studied in the human celiac/superior mesenteric ganglionic complex of pre- and full-term newborns, and adult subjects by means of immunohistochemistry. The antisera used labelled nerve fibres and terminal-like networks for each examined peptide, as well as VIP- and SOM-positive postganglionic neurons. Differences in the relative amount and density of the structures immunoreactive to the various peptides were observed. Moreover, variations in the amount and type of labelled elements were appreciable for each peptide when specimens from subjects at perinatal and adult ages were compared. Double-labelling immunofluorescence for SP and each other peptide showed that co-localization with SP is very frequent for CGRP, moderate to scarce for GAL and SOM, and rare to absent for PHI, VIP and ENK. VIP-, ENK- and CGRP-immunolabeled perikarya bearing the morphological features of the small intensely fluorescent (SIF) cells occurred in the organ. The presence of a paraganglion in one of the specimens examined allowed the detection of VIP- and ENK-positive cell bodies and VIP-, ENK-, SP- and GAL-like immunoreactive varicose nerve fibres in it. The results obtained provide substantial morphological data in support of the involvement of the examined peptides in the chemical interneuronal signalling in the human celiac/superior mesenteric ganglia.
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PMID:Neuropeptides in the human celiac/superior mesenteric ganglionic complex: an immunohistochemical study. 847 42

Tachykinin control of gut blood flow (measured by pulsed Doppler technique), dorsal aortic pressure, and heart rate were studied in unrestrained spiny dogfish Squalus acanthias injected with the elasmobranch tachykinins scyliorhinin I and II (SCY I and SCY II), the trout tachykinins substance P (SP), and neurokinin A (NKA). Effects on somatic vasculature were measured by in vitro perfusion of the isolated tail. SCY I and trout SP produced hypotension due to a general vasodilation. This caused a transient increase in mesenteric blood flow and a prolonged increase in celiac blood flow. SCY II caused an initial hypertension induced by a general vasoconstriction, followed eventually by an elevated flow in both gut arteries due to dilation of the vascular beds. Trout NKA evoked a short-lasting increase in celiac blood flow due to a decrease in vascular resistance, a late decrease in mesenteric flow due to vasoconstriction, and no effect on the somatic vasculature. None of the peptides affected heart rate. The study demonstrates a significant vasoactive function of fish tachykinins in the vascular system of an elasmobranch species and, in addition, the occurrence of tachykinin receptor subtypes. Immunohistochemistry revealed a NKA/SCY II-like peptide in nerve fibers innervating many vessels, including the celiac and the mesenteric arteries, the gastrointestinal canal, and the heart.
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PMID:Vasoactivity and immunoreactivity of fish tachykinins in the vascular system of the spiny dogfish. 878 Feb 24

The digestive system is densely innervated by calcitonin gene-related peptide (CGRP)-immunoreactive neurons. The present study investigated a) the distribution and origin of CGRP-immunoreactive fibers in the rat hepatobiliary tract, and b) their relation with substance P/tachykinin (SP/TK) immunoreactivity using immunohistochemical and radioimmunoassay techniques. CGRP-containing fibers form dense networks in the fibromuscular layer of the biliary tree and surrounding the portal vein. Thin, varicose fibers are present at the base of the mucosa of the ducts. In the liver, labeled fibers are restricted to the portal areas and the stromal compartment. Neonatal treatment with capsaicin, a neurotoxin for primary afferent neurons, or celiac/superior mesenteric ganglionectomy depletes CGRP-containing fibers in the biliary tract, and reduces those associated with the portal vein. In contrast, subdiaphragmatic vagotomy does not appreciably modify the density of these fibers. Radioimmunoassay studies show a reduction of CGRP-immunoreactive contents in the biliary tract and portal vein by 84% and 65%, respectively, following capsaicin treatment, and by 80% and 66%, respectively, following ganglionectomy. By contrast, CGRP concentrations in vagotomized animals are comparable to those of controls. Most CGRP-positive fibers appear to contain SP/TK immunoreactivity, as indicated by double-label studies. These results demonstrate that the rat hepatobiliary tract is prominently innervated by CGRP- and CGRP/SP/TK-immunoreactive fibers, which are likely to originate from spinal afferent neurons. The abundance of these fibers and their association with a variety of targets are in line with the involvement of these peptidergic visceral afferents in regulating hepatobiliary activities, including hemodynamic functions of the hepatic vasculature.
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PMID:Calcitonin gene-related peptide innervation of the rat hepatobiliary system. 880 23

Substance P (SP) is an important neurotransmitter in the control of intestinal motility and is found in both the enteric and sympathetic nervous systems. This study examined the effect of celiac ganglionectomy on (1) mechanical properties of the circular muscles of the duodenum, ileum and proximal colon, (2) circular muscle responses to SP and neurokinin A. (3) distribution of substance P-like immunoreactive nerves, and (4) the distribution of neurokinin 1 and neurokinin 2 receptors. Celiac ganglionectomy resulted in an effective sympathectomy as evidenced by a marked decrease in norepinephrine content and tyrosine hydroxylase staining in the duodenum, ileum and proximal colon. The in vitro length/tension characteristics of the circular muscle of the duodenum, ileum and colon were unchanged after ganglionectomy. In all regions of the gut studied, substance P and neurokinin A caused dose-dependent contractions that were unaltered by celiac ganglionectomy. Immunohistochemistry revealed moderate substance P-like immunoreactive fibers in the myenteric plexus, submucosal plexus and circular muscle of the ileum, while in the colon, substance P-like immunoreactivity was intense in the myenteric plexus, and moderate in the circular muscle. In vitro autoradiography showed minimal binding of SP (NK1 receptor) or neurokinin A (NK2 receptor) in the ileum and significantly greater binding in the circular muscle layer of the colon. Celiac ganglionectomy did not affect substance P-like immunoreactivity, or NK1 or NK2 receptor binding. A greater contractile response to neurokinins was seen in the colon than in the duodenum or ileum, which paralleled the receptor density. The studies demonstrate that surgical celiac ganglionectomy, unlike chemical sympathectomy, does not affect the substance P innervation, receptor density or physiological responses of the intestine. The greater contractile response of the colon than the ileum parallels the greater receptor density rather than the peptide content as determined by immunhistochemistry.
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PMID:Effect of celiac ganglionectomy on tachykinin innervation, receptor distribution and intestinal responses in the rat. 898 88

The work was carried out to investigate the relationship of non-cholinergic late slow excitatory potential (LS-EPSP) with 5-hydroxytryptamine (5-HT) and substance P (SP) in the neurons of the guinea pig celiac ganglion (CG) using intracellular electrodes in vitro. During repetitive stimulation of the splanchnic nerve (SN), LS-EPSP following a series of action potentials could be recorded in 161 out of 206 neurons (78.2%); Application of 5-HT and SP by superfusion or pressure ejection induced 5-HT depolarization in 102 out of 149 neurons (68.5%) and SP depolarization in 98 out of 188 neurons (52.1%), respectively; Most neurons, from which LS-EPSP could be recorded during stimulation of SN, were sensitive to 5-HT (73/88, 83.0%) and SP (68/114, 59.7%). However, only a small number of neurons not showing LS-EPSP during stimulation of SN were sensitive to 5-HT (10/26, 38.5%, P < 0.0001) and SP (11/36, 30.6%, P < 0.01). The results support the viewpoint that both 5-HT and SP are involved in the formation of LS-EPSP as transmitters; In addition, both effects of 5-HT and SP were examined in 133 neurons. There were 66 of these neurons (49.6%) to be sensitive to both 5-HT and SP, suggesting that there may be some functional relations between 5-HT and SP in the neurons of guinea pig CG.
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PMID:[The relationship of late slow excitatory potential with 5-hydroxytryptamine and substance P in the guinea-pig celiac ganglion]. 938 84

Peptidergic mechanisms influencing the resistance of the gastrointestinal vascular bed of the estuarine crocodile, Crocodylus porosus, were investigated. The gut was perfused in situ via the mesenteric and the celiac arteries, and the effects of different neuropeptides were tested using bolus injections. Effects on vascular resistance were recorded as changes in inflow pressures. Peptides found in sensory neurons [substance P, neurokinin A, and calcitonin gene-related peptide (CGRP)] all caused significant relaxation of the celiac vascular bed, as did vasoactive intestinal polypeptide (VIP), another well-known vasodilator. Except for VIP, the peptides also induced transitory gut contractions. Somatostatin and neuropeptide Y (NPY), which coexist in adrenergic neurons of the C. porosus, induced vasoconstriction in the celiac vascular bed without affecting the gut motility. Galanin caused vasoconstriction and occasionally activated the gut wall. To elucidate direct effects on individual vessels, the different peptides were tested on isolated ring preparations of the mesenteric and celiac arteries. Only CGRP and VIP relaxed the epinephrine-precontracted celiac artery, whereas the effects on the mesenteric artery were variable. Somatostatin and NPY did not affect the resting tonus of these vessels, but somatostatin potentiated the epinephrine-induced contraction of the celiac artery. Immunohistochemistry revealed the existence and localization of the above-mentioned peptides in nerve fibers innervating vessels of different sizes in the gut region. These data support the hypothesis of an important role for neuropeptides in the control of the vascular bed of the gastrointestinal tract in C. porosus.
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PMID:Peptidergic control of gastrointestinal blood flow in the estuarine crocodile, Crocodylus porosus. 984 48

The viral transneuronal labeling method was used to localize sympathetic-related neurons in the preoptic region following pseudorabies virus (PRV) injections into either the superior cervical ganglion, stellate ganglion, celiac ganglion, or adrenal gland of rats. A general pattern of infection was detected. First, neuronal labeling was found in the medial preoptic area, medial preoptic nucleus, median preoptic nucleus, and lateral preoptic area, and then it spread to the anteroventral periventricular, anteroventral preoptic, and parastrial nuclei. Finally, the forebrain circumventricular organs: organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO) became infected. Neuropeptide-containing preoptic neurons were analyzed following PRV injections in the stellate ganglion. Some thyrotropin-releasing hormone and neurotensin neurons were labeled, but none of the calcitonin gene-related peptide, cholecystokinin, corticotropin-releasing factor, galanin, luteinizing hormone-releasing hormone, enkephalin, substance P, or tyrosine hydroxylase neurons were PRV infected. Two major sympathetic networks appear to be represented in the preoptic region. One is linked to the OVLT, SFO, and anteroventral third ventricular (AV3V) region, sites previously implicated in fluid and electrolyte balance as well as cardiovascular control. The other descending sympathetic pathway appears to target the medial preoptic nucleus as its key nodal point, receiving inputs from infralimbic cortex and limbic regions, such as the lateral septum, medial nucleus of the amygdala, subiculum, and amygdalohippocampal area, and then, projecting caudally to the hypothalamus and brainstem. This second sympathetic network may subserve affiliative, defensive and sexual behaviors.
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PMID:Sympathetic-related neurons in the preoptic region of the rat identified by viral transneuronal labeling. 1051 2

Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children. Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches. We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance of triggers, prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder.
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PMID:Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder. 1095 42

The effects of endotoxin on gastric emptying of a solid nutrient meal and the neural mechanisms involved in such a response were investigated in conscious rats. The intraperitoneal (i.p.) administration of E. coli endotoxin (40 microg/kg) significantly reduced the 4-h rate of gastric emptying of a standard solid nutrient meal. Ablation of primary afferent neurons by systemic administration of high doses of capsaicin (20+30+50 mg/kg s.c.) to adult rats did not modify the rate of gastric emptying in control animals but prevented the delay in gastric transit induced by endotoxin. Local application of capsaicin to the vagus nerve rather than application of capsaicin to the celiac ganglion significantly repressed endotoxin-induced delay in gastric emptying. Neither treatment modified the rate of gastric emptying in vehicle-treated animals. Blockade of CGRP receptors (CGRP 8-37, 100 microg/kg i.v.) did not alter gastric emptying in control animals but significantly prevented endotoxin-induced inhibition of gastric emptying. In contrast, a tachykinin receptor antagonist ([D-Pro2, D-Trp7.9]-substance P, 2 mg/kg i.p.) significantly reduced the rate of gastric emptying in control animals and did not modify the inhibitory effects of endotoxin. Adrenergic blockade with phentolamine (3 mg/kg i.p.) +/- propranolol (5 mg/kg i.p.) or muscarinic antagonism with atropine (0.1 mg/kg i.p.) failed to reverse the delay in gastric emptying induced by endotoxin. These observations indicate that endotoxin-induced delay in gastric emptying of a solid nutrient meal is mediated by capsaicin-sensitive afferent neurons.
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PMID:Endotoxin inhibits gastric emptying in rats via a capsaicin-sensitive afferent pathway. 1128 41


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