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

The aim of the present study was to analyze the neurochemical properties of the centrifugal visual system (CVS) of the quail using an immunohistochemical approach by testing 16 neuropeptides (angiotensin: ANG, bradykinin: BK, cholecystokinin, dynorphin, L and M-enkephalin, beta-endorphin: beta-END, galanin, alpha-neoendorphin, neurokinin A, neuropeptide Y (NPY), ocytocin, somatostatin, substance P, vasopressin, vasoactive intestinal polypeptide) and three neurotransmitters or their synthetic enzymes (choline acetyltransferase: ChAT, tyrosine hydroxylase: TH, serotonin: 5-HT and nitric oxide synthase: NOS, including the histochemical nicotinamide adenine dinucleotide phosphate diaphorase technique). For each substance, the somatic and afferent fiber and terminal labeling was analyzed within the nucleus isthmo-opticus (NIO) and the ectopic area (EA) and compared with that of retinopetal cell bodies labeled retrogradely with RITC following its intraocular injection (double-labeling procedure). The results showed that none of the centrifugal neurons were reactive to any of the substances tested. In contrast, all with the exception of ANG, BK and beta-END, labeled fibers and terminals within the EA and only four (ChAT, 5-HT, NPY and NOS) within the NIO. Possible sources of these immunoreactive fibers terminating in the NIO and EA were investigated by mapping the somatic immunolabeling of the different substances within brainstem regions previously shown by Miceli and other authors to project upon the centrifugal neurons. The data suggests that, besides the rapid retino-tecto-NIO-retinal loop, which facilitates the transfer of meaningful or more relevant information within particular portions of the visual field, the multiple afferent input which stems from various brainstem regions utilizes a wide range of neuroactive substances. Some of these afferent projections upon the centrifugal neurons appear to belong to nonspecific systems which might play a role in modulating the excitability of centrifugal neurons as a function of arousal.
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PMID:An immunohistochemical study of putative neuromodulators and transmitters in the centrifugal visual system of the quail (Coturnix japonica). 971 61

In summary, PACAP exerts a biphasic effect (an initial contraction followed by a relaxation) in the IAS. The initial contractile effect with higher concentrations of PACAP was found to be mediated by the activation of PACAP receptor at the substance P-containing nerve terminals. The PACAP receptor(s) responsible for the inhibitory action of the neuropeptide is(are) hypothesized to be present in the IAS smooth muscle cells and on the myenteric nerve terminals. The exact nature and the role of PACAP and the PACAP receptors in the inhibitory neurotransmission, the relationship of PACAP receptors with substance P-containing neurons and IAS smooth muscle cells, and interactions with the NOS pathway and VIP remain to be determined.
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PMID:Sites of actions of contractile and relaxant effects of pituitary adenylate cyclase activating peptide (PACAP) in the internal anal sphincter smooth muscle. 992 59

The occurrence and colocalization of several biologically active neuropeptides, catecholamine-, acetylcholine- or nitric oxide-synthesizing enzymes-tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (D beta H), choline acetyl-transferase (ChAT) and nitric oxide synthase (NOS I), respectively, as well as the vesicular acetylcholine transporter (VAChT) were investigated in the penile glans (GP), corpus and crura (CP), as well as in the retractor penis muscle (RPM) of juvenile and adult boars. Immunohistochemistry revealed that nerves immunoreactive (IR) to TH, D beta H, vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) were the most numerous, followed (in decreasing order of density) by nerves IR to NOS, neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), galanin (GAL), Leu5-enkephalin (LENK) and ChAT/VAChT. The CP contained the largest number of nerve fibres followed by the RPM, GP and corpus. Enzyme/peptide-containing nerves were associated with both the vascular and non-vascular penile structures. However, differences existed for their density and intrapenile distribution. Nerve terminals IR for different combinations of VIP, GAL or SOM were more frequent than those IR for NOS or CGRP in the non-vascular penile structures while the vasculature and the RPM received a prominent TH/D beta H-, VIP-, SOM- or NOS-IR nerve input. The present data indicate that the porcine penis receives nerve fibres that exhibit diverse chemical codes and that differences in the chemical coding of the nerve fibres may depend on their penile target-structure.
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PMID:Innervation of the fibro-elastic type of the penis: an immunohistochemical study in the male pig. 1009 43

We recently reported that expression of recombinant endothelial nitric oxide (NO) synthase (eNOS) gene in adventitial fibroblasts restores NO formation in canine cerebral arteries without endothelium in response to bradykinin ex vivo and in vivo. The present study was designed to further characterize the stimuli that can activate recombinant eNOS enzyme expressed in the adventitia of cerebral arteries. To stimulate recombinant eNOS, we used serum (0. 1-10%), substance P (10(-11)-3 x 10(-9) M), and ANG II (10(-7)-10(-5) M) because they increase intracellular calcium concentrations in fibroblasts. Endothelium-denuded segments of canine basilar arteries were incubated with an adenoviral vector encoding beta-galactosidase gene or eNOS gene for 30 min at 37 degrees C. After 24 h, vasomotor activity and cGMP formation in eNOS or beta-galactosidase arteries were examined by isometric force recording and by radioimmunoassay, respectively. In control arteries and beta-galactosidase gene-transduced arteries, serum caused concentration-dependent contractions, whereas in recombinant eNOS gene-transduced arteries, serum produced concentration-dependent relaxations. Substance P and ANG II had no effect on vascular tone in control and beta-galactosidase arteries but caused concentration-dependent relaxations as well as a significant increase in cGMP levels in eNOS arteries. These relaxations were blocked by the NOS inhibitor NG-nitro-L-arginine methyl ester. Chemical treatment or mechanical inactivation of adventitial function significantly attenuated substance P-induced relaxations and ANG II-induced relaxations. These findings demonstrate that serum, substance P, and ANG II cause adventitia-dependent relaxations in cerebral arteries expressing the recombinant eNOS gene. This mechanism of vasodilatation may have beneficial effects in the prevention and treatment of vascular disorders characterized by the diminished bioavailability of NO, such as cerebral vasospasm.
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PMID:Adventitia-dependent relaxations of canine basilar arteries transduced with recombinant eNOS gene. 1051 60

Immunohistochemistry of normal eccrine sweat glands was performed on paraffin sections of human skin. Immunoreactivity (ir) for neuron specific enolase, S100 protein (S100), regulatory peptides, nitric oxide synthase type I (NOS-I) and choline-acetyltransferase (ChAT) was found in small nerve bundles close to sweat glands. In the glands, secretory cells were labelled with anticytokeratin antibody. Using antibodies to S100, calcitonin gene-related peptide (CGRP) and substance P (SP) a specific distribution pattern was found in secretory cells. Granulated (dark) and parietal (clear) cells were immunopositive for CGRP, and S100 and SP, respectively. Immunoreactivity was diffuse in the cytoplasm for CGRP and S100, and peripheral for SP. Myoepithelial cells were not labelled. Electron microscopy revealed electron dense granules, probably containing peptide, in granulated cells. Using antibodies to NOS-I and ChAT, ir was exclusively found in myoepithelial cells. Immunoreactivity for the atrial natriuretic peptide was absent in sweat glands. These results provide evidence for the presence of both regulatory peptides involved in vasodilation and key enzymes for the synthesis of nitric oxide and acetylcholine in the secretory coil of human sweat glands. It is suggested that human sweat glands are capable of some intrinsic regulation in addition to that carried out by their nerve supply.
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PMID:Immunohistochemical evidence suggests intrinsic regulatory activity of human eccrine sweat glands. 1038 80

Formation of mature active neuropeptides such as substance P (SP) from their glycine extended precursors entails alpha-amidation of peptide precursors by the sequential enzymatic action of peptidylglycine alpha-monooxygenase (PAM) and peptidylamidoglycolate lyase (PGL). We reported that these two enzymes that can produce mature active neuropeptides are present in cultured bovine aortic endothelial cells (BAECs). We hypothesize that alpha-amidation of peptides occurs in endothelial cells and that these peptides are critically involved in the overall regulation of cardiovascular function. In this study, this hypothesis was tested using specific amidation inhibitors to determine their effects on the actions of SP and its glycine-extended precursor (SP-Gly). We have found that SP and SP-Gly are equipotent in stimulating nitric oxide (NO) release by BAECs. At 10(-5) M, the specific inhibitors of PAM (4-phenyl-3-butenoic acid; PBA) and PGL (5-acetamido-2,4-diketo-6-phenyl-hexanoic acid and its methyl ester) reduced NO basal release by 40, 34, and 45%, respectively. They also reduced the production of NO induced by SP-Gly by 63, 68, and 69%, respectively, but had no effect on NO production in response to either SP or acetylcholine. SP and SP-Gly also were equipotent in relaxing rat aortic segments. The vasorelaxation to SP-Gly was endothelium dependent and inhibited by the NOS antagonist L-nitroarginine methyl ester (L-NAME), but it was not affected by inhibition of prostaglandin synthesis. Inhibitors of both PAM and PGL significantly reduced the vasorelaxing actions of SP-Gly, whereas responses to SP were not affected. A cumulative infusion of PBA into the femoral artery of rabbits, at final concentrations of 2.4, 24, and 240 microM for 20 min each, increased the vascular resistance (VR), indicating the tonic production of vasodilating amidated peptide(s). This effect was maximum at 60 min after infusion (20.5 +/- 4.7 vs. 8.2 +/- 0.7 mm Hg/ml/min; p < 0.05). These results suggest that endothelial cells can produce mature SP from its SP-Gly precursor and that a product of peptide alpha-amidation tonically stimulates endothelial cell NO release to control vascular tone.
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PMID:Vascular and endothelial actions of inhibitors of substance P amidation. 1083 20

A comparison of the localization of the neurokinin 1 (NK1) receptor and nitric oxide synthase with calbindin D labelling in the lumbar spinal cord was carried out in the rat using immunocytochemistry. Considerable regional variations were observed. Application of the antibody to calbindin D resulted in dense staining in laminae I and II and light staining in the other laminae. Occasional scattered cells were seen in the deep laminae and in the lamina X, the ventral horn and the lateral spinal nucleus. The results indicate that neurones expressing calbindin D, NK1 receptor and NOS are three separate populations in the dorsal horn of the lumbar spinal cord.
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PMID:Comparison of localization of the neurokinin 1 receptor and nitric oxide synthase with calbindin D labelling in the rat spinal cord. 1091 75

This study was conducted to determine the origin(s) of neuronal nitric oxide synthase-immunoreactive (NOS-IR) fibers within guinea pig atrial whole-mount preparations containing the cardiac ganglia. Intrinsic NOS-IR cardiac neurons exhibited choline acetyltransferase (ChAT) immunoreactivity, indicating that they were cholinergic as well as nitrergic. Comparison of control versus 72-hour explant culture preparations indicated that most of the nitrergic fibers within cardiac ganglia were extrinsic. The extrinsic NOS-IR fibers were not IR for ChAT (marker of preganglionic parasympathetic neurons), tyrosine hydroxylase (marker of catecholaminergic sympathetic postganglionic axons), or calcitonin gene-related peptide (CGRP) (marker of afferent fibers). Separate NOS-IR and ChAT-IR neurons were present within medullary regions containing the cardiovascular regulatory nuclei (nucleus ambiguus and dorsal motor nucleus of the vagus), but no cells were found that exhibited both NOS immunoreactivity and ChAT immunoreactivity. The small size and location of the medullary NOS-IR neurons suggested they were probably interneurons. Only an occasional sympathetic postganglionic cell in the stellate ganglion complex exhibited NOS immunoreactivity. NOS-IR cells were present in dorsal root ganglia (thoracic 1-5), but these typically also exhibited CGRP immunoreactivity. NOS-IR cells were also present in the nodose ganglia, but only some exhibited CGRP immunoreactivity. We concluded that virtually all the extrinsic NOS-IR nerve fibers represented an afferent fiber input that was separate from the substance P (SP)/CGRP-containing population of sensory fibers. Furthermore, much of this NOS innervation is probably derived from the nodose ganglia.
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PMID:Origin of neuronal nitric oxide synthase (NOS)-immunoreactive fibers in guinea pig parasympathetic cardiac ganglia. 1099 51

Since serotonin (5-HT) is implicated in exacerbating acute coronary syndromes, we studied the reactivity of atrial coronary arterioles (70-140 microm) of atherosclerotic patients undergoing cardiac surgery to 5-HT, substance P (Sub P), and sodium nitroprusside by video-microscopy. Before ischemia, 5-HT-induced relaxation was not affected by NS398 (cyclooxygenase inhibitor), H2O2 or U63557A (thromboxane A2 synthase inhibitor), but was reduced by L-NNA. 5-HT elicited a potent contractile response after ischemia that was inhibited by NS398, Indo, and U63557A. While Sub P relaxation was decreased after ischemia, SNP relaxation was unchanged. The mRNA steady-state levels of NOS-3, NOS-2, prostacyclin synthase, and COX- 1 were not altered by ischemia. COX-2 mRNA and protein levels (Westernblotting), however, were increased (mean +/- SEM) 2.4 +/- 0.4 and 3.2 +/- 0.7 fold, respectively, in ischemic atrium corroborating with the immunohistochemistry of atrial tissue. It is concluded that myocardial ischemia enhanced contractile response of coronary arterioles to 5-HT maybe due to the stimulated prostaglandin release (likely thromboxane A2) secondary to induction of COX-2 expression. These findings may have implications regarding the cause of coronary spasm during acute myocardial ischemia.
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PMID:Serotonin-induced human coronary microvascular contraction during acute myocardial ischemia is blocked by COX-2 inhibition. 1121 33

This study investigates whether nitric oxide (NO) is involved in the anxiogenic profile of action of substance P (SP) in mice in the elevated plus-maze (EPM). Adult Swiss mice were injected with NOS inhibitors such as L-NOARG (20 nmol/kg) i.p., L-NAME (3 nmol per site), 7-NI (0.25 nmol per site) i.c.v. or vehicle (NaCl 0.9% i.p. or PBS i.c.v.). About 30 min (i.p. pretreatment) or 5 min later (i.c.v. pretreatment), the animals received i.c.v. injections of SP (10 pmol) or phosphate buffered saline (PBS) (2 microl). Afterwards, they were observed in the EPM. SP per se reduced the time spent on open arms, an anxiogenic-like effect. This effect was reverted by different NOS inhibitors and the NO donor. NOS inhibitors had no influence on the EPM parameters but the NO-releasing compound SNAP, as well as its parent thiol NAP, increased the animals' locomotor activity. 8-Br-cGMP (20 nmol), a permeable cGMP analog, promoted an anxiogenic-like effect per se and enhanced the SP effect on the EPM. Altogether, these results suggest a putative NO role in the mediation of the anxiogenic-like effect of SP.
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PMID:Nitric oxide involvement in the anxiogenic-like effect of substance P. 1127 97


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