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)

(1) Circularly-oriented muscle strips from the human ileum responded to electrical field stimulation (1-50 Hz) with frequency-related primary relaxation at low frequency and primary contractions at high frequencies of stimulation. Both responses were abolished or markedly reduced by tetrodotoxin (1 microM). (2) Atropine (3 microM) or omega conotoxin (0.1 microM) reduced but dit not abolish contraction to electrical field stimulation and enhanced the relaxation. Omega conotoxin (0.1 microM) did not affect carbachol-induced contraction nor isoprenaline-induced relaxation. (3) Neurokinin A and substance P (1 nM-1 microM) produced a concentration-dependent contraction. The NK-1 receptor selective agonist, [Pro9]SP sulfone and the NK-2 receptor selective agonist [beta Ala8]NKA(4-10) produced a contraction superimposable to that of substance P and neurokinin A, respectively. On the other hand, [MePhe7]-neurokinin B, an NK-3 receptor selective agonist was ineffective up to 1 microM. The response to substance P or neurokinin A was unaffected by atropine (3 microM). (4) Galanin, up to 0.1 microM, produced a weak and inconsistent contraction. (5) Vasoactive intestinal polypeptide (10 nM-1 microM) produced a concentration-dependent relaxation while human alpha calcitonin gene-related peptide exerted a weak and inconsistent relaxant effect. (6) These findings indicate that both cholinergic excitatory and non-cholinergic inhibitory nerves affect the motility of the circular muscle of the human small intestine. Transmitter release from excitatory nerves seems largely mediated by activation of omega conotoxin-sensitive (N-type) calcium channels. Tachykinins exert a potent contractile effect, independently of cholinergic nerves, via NK-1 and NK-2 receptors.
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PMID:Human isolated ileum: motor responses of the circular muscle to electrical field stimulation and exogenous neuropeptides. 169 76

Following injection of retrograde tracer to one genitofemoral nerve of male rats, motoneurones and dorsal root ganglion cells of segmental levels L1/L2 were labelled ipsilaterally. Many labelled motoneurones were calcitonin gene-related peptide- (CGRP) immunoreactive. In the ganglia, a proportion of the labelled cells were CGRP-, tachykinin- or galanin-immunoreactive (10%:6%:53% respectively). In comparison with ganglia of the contralateral side, galanin-immunoreactive cells were significantly increased in the ipsilateral ganglia. Unilateral genitofemoral nerve section induced a loss of CGRP- or tachykinin- and an increase of galanin-immunoreactive cells in the ipsilateral L1/L2 ganglia. In the ipsilateral L1/L2 dorsal horn, CGRP and tachykinin, but not galanin, immunoreactivity was reduced. In the cremaster muscle and scrotal skin of either side galanin-immunoreactive fibres were not visible and CGRP- and tachykinin-immunoreactive fibres were depleted in the ipsilateral side. Capsaicin induced a loss of CGRP- and tachykinin-immunoreactive ganglion cells and of CGRP, tachykinin or galanin immunoreactivity from the dorsal horn. In the scrotal skin, CGRP- and tachykinin-immunoreactive fibres were depleted. By contrast in the muscle, a few CGRP-immunoreactive fibres persisted. The data demonstrate that (i) the genitofemoral nerve originates at segmental levels L1/L2; (ii) CGRP- and tachykinin-immunoreactive sensory and CGRP-immunoreactive motor neurones project to the cremaster muscle and scrotal skin; and (iii) nerve pertubation induces an increase of galanin-immunoreactive sensory neurones, the significance of which remains to be elucidated.
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PMID:Origins and projections of peptide-immunoreactive nerves in the male rat genitofemoral nerve. 169 68

In the search for novel antiproliferative agents for small cell lung cancer (SCLC), we found the neuropeptide antagonist [Arg6, D-Trp7,9,MePhe8]substance P(6-11) to be effective in vitro. In murine Swiss 3T3 cells [Arg6,D-Trp7,9,MePhe8]substance P(6-11) was identified as a potent inhibitor of vasopressin-stimulated DNA synthesis which also blocks [3H]vasopressin binding to specific cell-surface receptors. It was a less potent antagonist of gastrin-releasing peptide and bradykinin in these cells but did not block the effects of other mitogens. In SCLC cell lines, [Arg6,D-Trp7,9,MePhe8]substance P(6-11) inhibited colony-formation in soft agarose and growth in liquid culture in a dose-dependent manner. It also blocked receptor-mediated Ca2+ mobilization induced by vasopressin, bradykinin, cholecystokinin, galanin, gastrin-releasing peptide, and neurotensin. We suggest that broad-spectrum neuropeptide antagonists can block multiple autocrine and paracrine growth loops in SCLC and could be useful therapeutic agents.
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PMID:A neuropeptide antagonist that inhibits the growth of small cell lung cancer in vitro. 169 79

In addition to differences between the two submucosal ganglionic neural networks, i.e., the plexus submucosus externus (Schabadasch) and the plexus submucosus internus (Meissner), with respect to the occurrence and distribution of serotonin as neurotransmitter, immunocytochemistry also revealed a distinct distribution for various neuropeptides in these two plexuses. Immunoreactivity for galanin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, neuromedin U, enkephalin, somatostatin and neuropeptide Y was found in varicose and non-varicose nerve fibres of both submucosal ganglionic plexuses, albeit with a distinct distributional pattern. The difference in neurotransmitter and/or neuromodulator content between both neural networks became even more obvious when attention was focussed on the immunoreactivity of the nerve cell bodies for these substances. Indeed, neuropeptide Y, enkephalin- and somatostatin-immunoreactive neuronal perikarya as well as serotonergic neuronal cell bodies appear solely in the plexus submucosus externus. Neuromedin U-immunoreactive perikarya, mostly coexisting with substance P, are observed in large numbers in the plexus submucosus internus, whilst they are rare in the plexus submucosus externus. Double-labelling immunostaining for substance P with CGRP and galanin revealed a different coexistence pattern for the two submucosal ganglionic plexuses. The differing chemical content of the neuronal populations supports the hypothesis that the existence of the two submucosal ganglionic plexuses, present in most large mammals including man, not only reflects a morphological difference but also points to differentiated functions.
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PMID:Distinct distribution of CGRP-, enkephalin-, galanin-, neuromedin U-, neuropeptide Y-, somatostatin-, substance P-, VIP- and serotonin-containing neurons in the two submucosal ganglionic neural networks of the porcine small intestine. 169 6

The distribution and localization of several neuropeptides were investigated in the lichenified lesions of 11 patients with atopic dermatitis using indirect immunofluorescence. Substance P-positive nerve fibres were observed in most of the cases of atopic dermatitis, but not in normal controls. Somatostatin immunoreactive nerves were not found in the skin of atopic dermatitis, whereas a normal pattern of immunoreactivity could be detected in most of the healthy subjects. Neuropeptide Y-positive dendritic epidermal cells were observed in lesional skin from patients with atopic dermatitis, but not in controls. Calcitonin gene-related peptide and vasoactive intestinal polypeptide immunoreactivity in patients with atopic dermatitis did not differ from that in healthy subjects. With galanin antiserum a diffuse intracellular staining was observed in the epidermis of both atopic patients and controls, while no positive staining was found with either neurotensin or neurokinin A antibodies in either group. These findings suggest a possible involvement of some neuropeptides in the pathomechanisms of atopic dermatitis.
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PMID:Neuropeptides in skin from patients with atopic dermatitis: an immunohistochemical study. 169 5

The enteric neuropeptide galanin (GAL) increased the amplitude of spontaneous contractions in longitudinally oriented muscle strips and inhibited short-circuit current (Isc) elevations induced by transmural electrical stimulation (ES) of mucosal sheets from porcine jejunum in vitro. GAL-induced contractions (GAL EC50 = 9 nmol/l) were maximally 25% of those elicited by 10 mumol/l carbamylcholine and remained unaffected by atropine, tetrodotoxin, or tachyphylaxis to substance P. The presynaptic Ca2+ channel blocker, omega-conotoxin (0.1 mumol/l), inhibited GAL-induced contractions by 66%. GAL attenuated mucosal Isc elevations induced by ES with an IC50 = 13 nmol/l and at 0.1 mumol/l produced rapid decreases in basal Isc averaging 8 +/- 2 microA cm-1 in 77% of tissues examined. The alpha-adrenoceptor blocker phentolamine or the opiate antagonist naloxone did not alter tissue Isc responses to GAL. These results suggest that GAL modulates neuronal activity linked to secretomotor function in the porcine small intestine.
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PMID:Effects of galanin on smooth muscle and mucosa of porcine jejunum. 169 75

The biological activity of two galanin (GAL) fragments, GAL-(1-16) and GAL-(17-29), was tested in vivo by using a spinal nociceptive flexor reflex model in the rat. Intrathecal (i.t.) GAL-(1-16) had a similar biphasic effect on the flexor reflex, with facilitation at lower doses and facilitation followed by depression at higher doses, as the full length peptide GAL-(1-29). GAL-(1-16) also effectively depressed the facilitation of the flexor reflex caused by i.t. substance P (SP) or C-fiber conditioning stimulation (CS) and potentiated the depressive effect of i.t. morphine on the reflex, both actions that have been reported earlier with GAL-(1-29). In contrast, i.t. GAL-(17-29), even at high doses, did not induce changes in the amplitude of the flexor reflex, nor did it interact with the effects of i.t. SP, morphine or C-fiber CS. It is concluded that the N-terminal portion of GAL-(1-29) is critical for the biological activity of the intact peptide in the dorsal horn of the rat spinal cord. The similarity between the effects of GAL-(1-16) and GAL-(1-29) indicates that they probably act on the same GAL receptor.
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PMID:The N-terminal 1-16, but not C-terminal 17-29, galanin fragment affects the flexor reflex in rats. 169 60

Immunocytochemical double and triple staining techniques were employed on whole mounts of the submucosal plexus from normal Wistar and non-diabetic BB rat jejunum and ileum, to determine the patterns of co-localization of vasoactive intestinal polypeptide-, peptide histidine-isoleucine-, somatostatin-, neuropeptide Y-, calcitonin gene-related peptide-, substance P-, and galanin-immunoreactive nerves. Neuropeptide Y immunoreactivity was found in 38% of submucosal plexus neurons, within the same neuronal elements as vasoactive intestinal polypeptide immunoreactivity (39% of submucosal plexus neurons) and peptide histidine-isoleucine immunoreactivity. A small population (1% of submucosal plexus neurons) containing vasoactive intestinal polypeptide- and peptide histide isoleucine-like immunoreactivity without NPY-like immunoreactivity was also observed. A significant population of fibers containing vasoactive intestinal polypeptide and galanin immunoreactivity were observed in the mucosa and submucosa, although no cell bodies were detected which contained both neuropeptides. Galanin-like immunoreactivity was seen in a small (2% of submucosal plexus neurons) population, not co-localized with any of the other neuropeptides examined. All somatostatin-immunoreactive neuronal elements (18% of submucosal plexus neurons) contained calcitonin gene-related peptide immunoreactivity, just over half of which also contained substance P immunoreactivity. An additional 25% of submucosal plexus neurons contained calcitonin gene-related peptide- without somatostatin-like immunoreactivity and 28% of submucosal plexus neurons contained substance P without somatostatin-like immunoreactivity. Some degree of co-localization was seen between calcitonin gene-related peptide- and substance P-like immunoreactivity, however, this could not be directly quantified.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The co-localization of neuropeptides in the submucosa of the small intestine of normal Wistar and non-diabetic BB rats. 169 58

A depletion of large cholinergic neurons in the nucleus basalis of Meynert is a consistent finding in Alzheimer's disease (AD). The nucleus basalis of Meynert also contains interneurons and afferents that may modulate its functioning. In the present study we examined neurochemical markers for neuropeptides, amino acid neurotransmitters, and monoaminergic neurotransmitters in postmortem samples of the nucleus basalis in 16 control subjects and 30 patients with AD. There were no significant changes in glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and catecholamines; however, concentrations of serotonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol were significantly reduced. Choline acetyltransferase activity was significantly reduced, consistent with previous reports. Galanin immunoreactivity was significantly increased twofold in the patients with AD, but there were no significant changes in substance P, somatostatin, or neuropeptide Y immunoreactivity. Since galanin inhibits acetylcholine release, and produces cognitive deficits in animals, increased galanin immunoreactivity in the nucleus basalis of Meynert in AD may contribute to the cognitive deficits that characterize the illness.
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PMID:Galanin immunoreactivity is increased in the nucleus basalis of Meynert in Alzheimer's disease. 169 71

1. Rat and porcine galanin (rGal and pGal) produced dose-dependent contraction of rat fundus strips in a concentration range of 6 nM-100 nM. 2. The stimulatory effect of rGal on rat fundus strips was not modified in the presence of somatostatin (250 nM), naloxone (1 microM), guanethidine (10 microM), a mixture of propranolol (3 microM) and phentolamine (3 microM), tetrodotoxin (1 microM), indomethacin (10 microM), atropine (1 microM), a mixture of methysergide (2.5 microM) and ketanserine (2.5 microM), a mixture of mepyramine (10 microM) and cimetidine (10 microM), and saralasin (10 microM) or when strips were desensitized to substance P and neurotensin. 3. These results suggest the localization of specific Gal receptors on the surface of smooth muscle cells of rat fundus. 4. The galanin analogues [D-Trp2]-rGal, [Nle4]-rGal, [D-Ala7]-rGal, [D-Trp2-NLe4-D-Ala7]-rGal and fragments [Cys23]-Gal (1-23), Gal (1-18) were fully active. In contrast, rGal (3-29) was completely inactive and showed no antagonistic properties to the contractile effect of intact galanin. 5. The order of potency of the galanin peptides, analogues and fragments to contract rat fundus strips was: pGal greater than rGal greater than [NLe4]-rGal greater than [Cys23]-Gal (1-23) greater than Gal (1-18) greater than [D-Ala7]-rGal greater than [Trp2]-rGal greater than [D-Trp2-NLe4-D-Ala7]-rGal. 6. The data originating from our structure-activity study suggest that the C-terminal portion of Gal contributes mainly to the affinity of Gal receptors whereas the N-terminal portion of Gal is responsible for the full activation of Gal receptors in this tissue. In particular the amino acids in position 1 and 2 of Gal (Gly-Trp) appear to be essential for binding and intrinsic activity.
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PMID:Effects of galanin, its analogues and fragments on rat isolated fundus strips. 170 74


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