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)

A study in cats has shown that intracameral injection of calcitonin gene-related peptide (CGRP) increases the outflow facility by four- to fivefold concomitant with a decrease in intra-ocular pressure (IOP). Since there are great differences in the anatomy of the aqueous outflow routes between cats and primates, we have examined the effects of CGRP in the cynomolgus monkey. The possible influence of the sensory neuropeptides cholecystokinin (CCK), galanin and substance P on the outflow facility and IOP were also investigated. Determinations were performed using a two-level constant-pressure procedure. At 40-60 min after intracameral injection of 3 micrograms CGRP the outflow facility was increased from 0.68 +/- 0.11 to 1.03 +/- 0.15 microliters min-1 mmHg-1 in the CGRP-treated eyes, and from 0.71 +/- 0.12 to 0.79 +/- 0.10 microliter min-1 mmHg-1 in the control eyes. The mean difference in increase was 0.27 +/- 0.06 microliter min-1 mmHg-1 (P less than 0.01, n = 7). During the experiments there was a small rise in the IOP. CGRP at a dose of 3 micrograms caused a small rise in aqueous humor protein concentration. An attempt to release endogenous CGRP with capsaicin did not result in an increased outflow facility. Three micrograms each of CCK, galanin and substance P had no significant effect on either the outflow facility or the IOP. A miosis was observed in the experiments with CCK in agreement with previous findings. CCK seems thus to cause contraction of the pupillary sphincter but does not influence the ciliary muscle sufficiently to cause a facility effect in the monkey eye.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Outflow facility in the monkey eye: effects of calcitonin gene-related peptide, cholecystokinin, galanin, substance P and capsaicin. 170 89

The ability to assess the importance of secretin in various physiological processes is limited by the lack of specific potent antagonists. Recently, reduced peptide bond (psi) analogues of bombesin or substance P in which the -CONH- bond is replaced by -CH2NH- are reported to be receptor antagonists. To attempt to develop a new class of secretin receptor antagonists, we have adopted a similar strategy with secretin and sequentially altered the eight NH2-terminal peptide bonds, the biological active portion of secretin. In guinea pig pancreatic acini, secretin caused a 75-fold increase in cyclic AMP (cAMP). Secretin inhibited 125I-secretin binding with a half-maximal effect at 7 nM. Each of the psi analogues inhibited 125I-secretin binding. [psi 4,5]Secretin was the most potent, causing the half-maximal inhibition at 4 microM, and was 2-fold more potent than the [psi 1,2]secretin; 7-fold more than [psi 3,4]secretin, [psi 5,6]secretin, and [psi 8,9]secretin; 9-fold more than [psi 7,8]secretin; 13-fold more potent [psi 6,7]secretin, and 17-fold more than [psi 2,3]secretin. Secretin caused a half-maximal increase in cAMP at 1 nM. At concentrations up to 10 microM, [psi 2,3]secretin, [psi 4,5]secretin, and [psi 8,9]secretin did not alter cAMP whereas [psi 1,2]secretin and [psi 6,7]secretin caused a detectable increase in cAMP at 10 nM, [psi 7,8]secretin at 300 nM, [psi 5,6]secretin at 1 microM, and [psi 3,4]secretin at 10 microM. The [psi 4,5], [psi 2,3], and [psi 8,9] analogues of secretin each inhibited 1 nM secretin-stimulated cAMP as well as [psi 3,4]secretin, which functioned as a partial agonist. [psi 4,5]Secretin was the most potent, causing half-maximal inhibition at 3 microM whereas [psi 8,9]secretin was 6-fold less potent, and [psi 2,3]secretin and [psi 3,4]secretin were 17-fold less potent. [psi 4,5]Secretin inhibited secretin-stimulated cAMP and binding of 125I-secretin in a competitive manner. [psi 4,5]Secretin did not interact with cholecystokinin, bombesin, calcitonin gene-related peptide, or cholinergic receptors but did interact with receptors for vasoactive intestinal peptide, causing half-maximal inhibition at 72 microM and thus had a 18-fold higher affinity for secretin than vasoactive intestinal peptide receptors. These results indicate that reduced peptide bond analogues of the NH2 terminus of secretin represent a new class of secretin receptor antagonists. It is likely that in the future even more potent members of this class can be developed which may be useful to investigate the role of secretin in various physiological processes.
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PMID:Reduced peptide bond pseudopeptide analogues of secretin. A new class of secretin receptor antagonists. 170 23

In order to study the effects of a neonatal dopamine lesion on dopaminergic, serotonergic and peptidergic systems, Sprague-Dawley rats were treated by intracerebroventricular administration of 6-hydroxydopamine (100 micrograms, days 3 and 6) following desipramine pretreatment (25 mg/kg s.c.). At 60-70 days postnatally a profound reduction of dopamine- and 3,4-dihydroxyphenylacetic acid levels was found in striatal and limbic forebrain regions concomitant with an extensive loss of tyrosine hydroxylase-immunoreactive fibers, while no significant alteration in noradrenaline levels was seen. A marked loss of tyrosine hydroxylase-immunoreactive cell profiles was also observed in the substantia nigra and ventral tegmental area in mesencephalon. In striatum, but not in other regions analysed, an almost 100% increase in serotonin levels and serotonin-immunoreactive fiber density was observed following 6-hydroxydopamine treatment. However, the number of serotonin-immunoreactive cell profiles in the median and dorsal raphe nuclei was not altered. The 6-hydroxydopamine treatment also led to reductions in substance P levels in striatum, nucleus accumbens and ventral mesencephalon. The cholecystokinin level in nucleus accumbens and neurotensin level in ventral mesencephalon were also reduced. A neonatal intracerebroventricular 6-hydroxydopamine treatment thus leads to a lesion of dopamine neurons in the mesencephalon with extensive loss of dopamine fibers in several forebrain areas, while localized serotonin fiber sprouting is induced in striatum. Furthermore, concomitant reductions of the levels of peptides related to the dopamine system occur following the 6-hydroxydopamine treatment. Behavioral disturbances such as hyperactivity and cognitive deficiencies occurring after a dopamine lesion early in life might therefore be due to plastic alterations in several different transmitter/neuromodulator systems as a direct or indirect consequence of the lesion.
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PMID:Studies on brain monoamine and neuropeptide systems after neonatal intracerebroventricular 6-hydroxydopamine treatment. 170 72

The peroxidase-antiperoxidase method was used to examine major immunohistochemical features of the spinal cord of adult raccoons. The lateral portions of the ventral horn contained many large multipolar neurons that showed cholecystokinin-like immunoreactivity, suggesting the coexistence of cholecystokinin with acetylcholine in a subset of motoneurons. The dorsal horn revealed unique but overlapping patterns of immunoreactivity for glutamic acid decarboxylase, somatostatin, substance P, vasoactive intestinal polypeptide and cholecystokinin. The data imply that some of the peptides may coexist within the same dorsal root ganglion cells and their spinal cord processes.
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PMID:Immunoreactivity for glutamic acid decarboxylase and several neuropeptides in the spinal cord of the raccoon. 170 58

We studied smooth muscle strips from rabbit distal colon to determine age-related changes in length-tension properties and agonist-mediated contraction. Strips from newborn (1-d-old) and weanling (11-wk-old) rabbits were oriented to measure isometric tension in longitudinal muscle. Active tension comprised 47 +/- 4 and 75 +/- 5% of the total tension in the newborn and weanling, respectively. Total and active tensions in the weanling were greater than in the newborn (p less than 0.001). Although the potencies for bethanechol were similar, the maximal response was nearly 9-fold greater in weanlings (6900 +/- 292 mN/cm2) versus newborns (753 +/- 112 mN/cm2), p less than 0.001. Maximal stress increased with age for bethanechol, high extracellular potassium, substance P, neurokinin A, cholecystokinin octapeptide, bombesin, and serotonin. ED50 for bethanechol, substance P, neurokinin A, and bombesin did not change with age. Serotonin was 12 times more potent in newborns versus weanlings (p less than 0.05). In contrast, cholecystokinin octapeptide was five times less potent in newborns (18.6 nM versus 3.4 nM, respectively, p less than 0.05). Substance P-induced contractions were inhibited partially by atropine. We conclude that length-tension properties of longitudinal colonic smooth muscle differ, and responses to agonists increase with age.
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PMID:Developmental changes in agonist-mediated colonic smooth muscle contraction in the rabbit. 170 95

We studied the role of gastrin-releasing peptide (GRP) for porcine gallbladder motility. Immunohistochemistry visualized nerve fibers containing GRP-like immunoreactivity in muscularis. GRP concentration dependently stimulated contractions of muscularis strips (ED50, 2.9 nM). Neuromedin B was less potent (ED50, 0.1 microM), suggesting existence of GRP-preferring receptors. GRP-induced contractions were unaffected by muscarinic antagonism (1 microM atropine), axonal blockade (1 microM tetrodotoxin), cholecystokinin (CCK) receptor antagonism (10 microM MK-329), or substance P desensitization (1 microM), supporting the existence of myogenic GRP receptors. The bombesin (BN) analogue D-Phe6-BN-(6-13)propylamide (PA) stimulated contractions (ED50, 3.3 nM) with low efficacy (29% of that of GRP). D-Phe6-BN-(6-13)PA (1 microM) shifted GRP concentration-response curves one log to the right. D-Phe6-BN-(6-13)PA interacted specifically with GRP receptors; while abolishing responses to GRP (1 nM), responses to substance P (0.1 microM) and CCK-8 (1 nM) were unchanged. Electrical stimulation (10 Hz, 0.5 ms, 10 V) caused a rapid onset-slow offset, tetrodotoxin-sensitive excitation. Atropine reduced the amplitude to 58% and caused a delayed, slow onset-slow decline response. D-Phe6-BN-(6-13)PA reduced the amplitude to 59% and caused a very rapid onset-rapid decline response. Atropine plus D-Phe6-BN-(6-13)PA abolished responses to nerve stimulation. Nerve stimulation caused significant release of GRP-like immunoreactivity. Thus two neural inputs were defined: a cholinergic rapid onset-rapid offset excitation and a delayed, slow onset-slow offset excitation caused by release and subsequent binding of GRP to GRP-preferring receptors.
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PMID:Gastrin-releasing peptide is a transmitter mediating porcine gallbladder contraction. 170 7

We examined the changes in the concentrations of neuropeptides in various regions of the mouse brain 1, 2 or 6 weeks after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/kg i.p. twice/day for 5 days) and further examined the effects of levodopa injections (200 mg/kg i.p.) for 14 days starting 4 weeks after MPTP treatment on regional somatostatin (SRIF) concentrations. Substance P, cholecystokinin-octapeptide and thyrotropin-releasing hormone did not show any significant changes up to 6 weeks after MPTP treatment, whereas the SRIF concentration increased 1 week after MPTP treatment but decreased thereafter, showing a marked decrease in the striatum and hippocampus after 6 weeks. In the striatum, the decreased concentration of SRIF recovered to the normal level with levodopa injections. This SRIF depletion could be a change secondary to dopamine depletion. On the other hand, in the cerebral cortex, while showing no change in the SRIF concentration after MPTP treatment, the concentration decreased significantly with levodopa injections. In the hippocampus, the decreased SRIF levels were still low after levodopa treatment. Since it has been reported that SRIF concentrations are significantly reduced in the frontal cortex and hippocampus of demented parkinsonians and patients with senile dementia of the Alzheimer type and that levodopa treatment induced various psychiatric side effects, the results of the present study suggest some relationship among levodopa treatment, SRIF depletion and the demented state.
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PMID:Alterations of somatostatin and its modulation by levodopa in MPTP-treated mouse brain. 170 6

In situ hybridization was used to determine whether genes for neuropeptides [substance P/neurokinin A (SP/NKA), calcitonin gene-related peptide (CGRP), somatostatin (SOM), neuropeptide tyrosine (NPY) and cholecystokinin (CCK)] are expressed in inferior ganglia of the vagus (nodose) and glossopharyngeal (petrosal) nerves. Synthetic oligodeoxyribonucleotides, complementary to the cognate, mRNAs were labeled with [32P] or [35S], and hybridized to 10 microns thick sections of unperfused tissue which were then processed for film and emulsion autoradiography. We found numerous, clustered neuronal perikarya throughout the nodose and petrosal ganglia that expressed preprotachykinin A (SP/NKA) and CGRP mRNAs to varying degrees. Neurons expressing preproSOM mRNA were less abundant and more scattered throughout both ganglia. Notably, we found mRNA for NPY in cells (usually 5-10 per section) in both ganglia. To our knowledge, this is first evidence for NPY in these sensory ganglia. In contrast to previous immunohistochemical findings, we found no evidence for expression of preproCCK in either the nodose or petrosal ganglia. The present findings demonstrate that cells of the nodose and petrosal ganglia express the genes for a number of neuropeptides that are presumably involved with transmission of visceral sensory afferent information to higher order neurons of the central nervous system.
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PMID:Gene expression for peptides in neurons of the petrosal and nodose ganglia in rat. 170 26

The distribution of chromogranin A (CgA), a soluble protein in dense-core synaptic vesicles expressed by a variety of neuronal cell types, was studied immunocytochemically in Alzheimer's disease and normal aging. In addition to its presence in neuronal perikarya and process, CgA-like immunoreactivity (CgA-li) was demonstrated in multiple dystrophic neurites forming the crown of senile plaques. Two different monoclonal antibodies, LK2H10 and PHE5, gave identical results. In the two regions of the brain studied--the calcarine cortex and the molecular layer of the dentate gyrus--the areal density of plaques associated with CgA-like immunoreactive neurites was greater than the density of Congo red-stainable amyloid cores, but smaller than the density of beta amyloid peptide deposits identified by the Campbell silver stain. By comparison, other synaptically released peptides--somatostatin 28, somatostatin 14, substance P, cholecystokinin, neurotensin, vasoactive intestinal peptide, and leu-enkephalin--were immunocytochemically detected in less than 30% of plaques. Thus CgA appears unique among known synaptically released substances in being present in dystrophic neurites in virtually all classic (i.e., Congo red stainable) plaques and additionally in a subpopulation of preamyloid plaques.
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PMID:Chromogranin A-like immunoreactive neurites are major constituents of senile plaques. 171 Jul 35

Anterograde tracing studies were conducted in order to identify efferents from the arcuate nucleus, which contains the hypothalamic opiocortin neuronal pool. Phaseolus vulgaris leucoagglutinin (PHA-L) was stereotaxically iontophoresed into the arcuate nucleus and the terminal fields emanating from the labelled perikarya were identified immunocytochemically. PHA-L-immunoreactive (-ir) fibers were identified in nucleus accumbens, lateral septal nucleus, bed nucleus of the stria terminalis, medial and lateral preoptic areas, anterior hypothalamus, amygdaloid complex, lateral hypothalamus, paraventricular nucleus, zona incerta, dorsal hypothalamus, periventricular gray, medial thalamus and medial habenula. In the brainstem, arcuate terminals were identified in the periaqueductal gray (PAG), dorsal raphe nucleus (DRN), nucleus raphe magnus (NRM), nucleus raphe pallidus, locus coeruleus, parabrachial nucleus, nucleus reticularis gigantocellularis pars alpha, nucleus tractus solitarius and dorsal motor nucleus of the vagus nerve. Dual immunostaining was used to identify the neurochemical content of neurons in arcuate terminal fields in the brainstem. Arcuate fiber terminals established putative contacts with serotonergic neurons in the ventrolateral PAG, DRN and NRM and with noradrenergic neurons in periventricular gray, PAG and locus coeruleus. In the PAG, arcuate fibers terminated in areas with neurons immunoreactive to substance P, neurotensin, enkephalin and cholecystokinin (CCK) and putative contacts were identified with CCK-ir cells. This study provides neuroanatomical evidence that putative opiocortin neurons in the arcuate nucleus influence a descending system which modulates nociception.
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PMID:Arcuate nucleus projections to brainstem regions which modulate nociception. 171 59


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