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)

Spontaneous rhythmic activity, responses to drugs and effects of field stimulation of nerves of the retractor penis (rp) and/or corpus cavernosum urethrae (ccu) of macaque, rabbit, guinea-pig, rat, dog, cat, horse, boar, elk, bull, ram and goat, as well as of the penile artery (pa) of bull were studied. A basic property of all these muscles was automaticity. Their responses to 5-hydroxytryptamine, histamine, adenosine triphosphate, prostaglandins E1, E2, AND F2alpha, oxytocin, vasopressin, substance P, bradykinin and angiotensin exhibited considerable species variations. Their excitatory innervation seems to be adrenergic. They also have an inhibitory innervation. In spite of comprehensive pharmacological analysis the inhibitory mediator remains obscure. The frequency--response relationship to inhibitory nerve stimulation was characterized by a rapidly achieved maximum at low frequencies, indicating high efficiency of the neuroeffector unit.
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PMID:Comparative study of some isolated mammalian smooth muscle effectors of penile erection. 92 Feb 6

The fate of serotonin and substance P receptors following serotonin/substance P hyperinnervation of CNS tissue was investigated in the inferior olivary complex of adult rats subjected to earlier intraventricular administration of 5,6-dihydroxytryptamine. [3H]8-hydroxy-2-(Dl-n-propylamino)tetralin, [3H]5-hydroxytryptamine, [3H]ketanserin and [125I]Bolton-Hunter-substance P were respectively used to label 5-hydroxytryptamine1A, 5-hydroxytryptamine1B, 5-hydroxytryptamine2 and neurokinin-1 receptor sites for quantitative ligand binding autoradiography. Only 5-hydroxytryptamine2 and neurokinin-1 sites were detected in the normal or serotonin/substance P-hyperinnervated inferior olivary complex. In the normal inferior olivary complex, the density of [3H]ketanserin binding (5-hydroxytryptamine2 receptors) was relatively low, being the highest in pars a of the caudal medial accessory olive and the principal olive; moderate in pars c of the caudal medial accessory olive; truly low in the medial and the lateral dorsal accessory olive, nucleus b and pars b of the caudal medial accessory olive; and negligible in the middle medial accessory olive, rostral medial accessory olive and the smaller subnuclei. [125I]Bolton-Hunter-substance P binding (neurokinin-1 receptors) appeared denser, being highest in nucleus beta and the middle medial dorsal accessory olive; moderate in the three portions of the caudal medial accessory olive, the lateral dorsal accessory olive and the dorsal cap of Kooy; low in the rostral medial accessory olive, the ventrolateral outgrowth and the dorsomedial cell column; and very low or null in the principal olive and the medial dorsal accessory olive. After serotonin/substance P hyperinnervation, there were striking increases in the apparent density of both populations of receptor. [3H]Ketanserin binding was now stronger in the most olivary subnuclei, including some in which it had not been found in the normal, such as the middle and the rostral medial accessory olive. [125I]Bolton-Hunter-substance P binding showed even greater elevations in a few subnuclei, such as the principal olive and the dorsomedial cell column; it was now detectable in the medial dorsal accessory olive, unchanged in the dorsal cap of Kooy and the ventrolateral outgrowth, and slightly decreased in the lateral dorsal accessory olive. The normal and altered distributions of both ligands did not match the respective patterns of serotonin and substance P innervation and hyperinnervation previously demonstrated with immunocytochemistry. In some sectors of the inferior olivary complex where both transmitters are presumably co-localized, there was no overlap in the distribution of the respective binding sites either in the normal or in the hyperinnervated state.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Up-regulation of 5-hydroxytryptamine2 and neurokinin-1 receptors associated with serotonin/substance P hyperinnervation in the rat inferior olive. 128 26

1. A study was made of the pelvic and the splanchnic nerve supplies to the toad large intestine. 2. Stimulation of pelvic nerve fibres in the 9th and 10th spinal nerves caused a series of contractions of the circular muscle, only the first of which was abolished by hyoscine. The entire response was blocked by d-tubocurarine. The response was not affected by capsaicin treatment. 3. Stimulation of the splanchnic nerves caused a rapid contraction followed by a prolonged relaxation. The relaxation was abolished by bretylium. The contraction was selectively antagonised by prolonged exposure to capsaicin. Splanchnic nerve stimulation also caused a slow, prolonged excitation that was abolished by bretylium. 4. Application of adrenaline caused relaxation of circularly cut strips of large intestinal wall, whereas substance P, acetylcholine, 5-hydroxytryptamine, somatostatin and galanin caused contraction. 5. The results suggest that stimulation of the pelvic nerves releases acetylcholine and a non-cholinergic co-transmitter from peripheral postganglionic neurons. Both the inhibitory response to splanchnic nerve stimulation and the subsequent slow excitation appear to be mediated by adrenergic nerves. The rapid capsaicin-sensitive excitation is likely to be due to release of substance P from antidromically activated afferent nerve fibres in the splanchnic outflow.
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PMID:The autonomic innervation of the large intestine of the toad (Bufo marinus). 135 34

Previous studies by other investigators have shown that neonatal administration of high doses of L-cysteine produces within 6 hrs morphological damage to neurons in many areas of the brain including the striatum; the damage could be blocked by NMDA antagonist MK-801. These studies implicated a potential involvement of this amino acid in neurodegenerative processes including Parkinsonism. The present study attempted to elucidate whether L-cysteine produces long-term changes in neurotransmitter (dopamine; 5-hydroxytryptamine) or neuropeptide (Met5-enkephalin; dynorphin A (1-8); substance P) systems as a corollary to neonatal treatment with L-cysteine. L-cysteine (0.5 or 1 g/kg, s.c.) was administered to 4-day old rat pups and sacrificed 35 days later. The striatal levels of amines and neuropeptides were determined by HPLC and radioimmunoassay respectively. L-Cysteine treatment alone or after a pretreatment with MK-801 (1 mg/kg, s.c.) failed to produce any significant changes in the parameters studied. The results indicate that neonatal administration of L-cysteine does not appear to produce long-term effects on major neuroregulator systems of the striatum.
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PMID:Neonatal administration of L-cysteine does not produce long-term effects on neurotransmitter or neuropeptide systems in the rat striatum. 135 16

Specimens of the sigmoid colon were obtained from male and female patients (n = 11) with carcinoma of the colon or rectum and studied immunohistochemically for vasoactive intestinal polypeptide-, somatostatin-, substance P-, neuropeptide Y-, calcitonin gene-related peptide-, met- and leu-enkephalin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-containing nerves. In the subdivisions of the submucous plexus (namely, Schabadasch's, Meissner's, and the intermediate plexuses), substance P- and vasoactive intestinal polypeptide-immunoreactive nerve fibers were the most numerous, and equal densities of these nerves were found in all three layers. In contrast, few neuropeptide Y-, met-enkephalin-, leu-enkephalin-, calcitonin gene-related peptide-, somatostatin-, 5-hydroxytryptamine-, and dopamine beta-hydroxylase-immunoreactive nerves were found in these regions. The nerve cell bodies of the submucous plexus contained vasoactive intestinal polypeptide, substance P, leu-enkephalin, somatostatin, and 5-hydroxytryptamine but not neuropeptide Y, met-enkephalin, calcitonin gene-related peptide, and dopamine beta-hydroxylase. Vasoactive intestinal polypeptide-containing nerve cell bodies were found in all three subdivisions. Substance P-, leu-enkephalin-, and somatostatin-immunoreactive nerve cell bodies were found in Schabadasch's plexus and the intermediate region of the submucous plexus, but they were absent from Meissner's plexus; 5-hydroxytryptamine-containing nerve cell bodies were only observed in Schabadasch's plexus. The possible function of the neuropeptide-, dopamine beta-hydroxylase-, and 5-hydroxytryptamine-containing neurons in the different layers of the submucous plexus is discussed.
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PMID:Peptide-containing neurons in different regions of the submucous plexus of human sigmoid colon. 848 77

1. To examine the role of epithelium in the responsiveness of tracheal smooth muscle in rabbit, we measured the contractile responses to acetylcholine (ACh), KCl, 5-hydroxytryptamine (5-HT), histamine, substance P (SP), neurokinin A (NKA), and electrical field stimulation EFS) in intact and epithelium-denuded preparations. 2. Removal of epithelium did not alter the contractile response to any agonist examined, except SP. 3. Removal of epithelium enhances the contractile response to SP. In the presence of phosphoramidon, the contractile response to SP was not significantly different in either group. The results suggest that the effect of epithelium is largely due to degradation of SP by enzymes in the epithelium. 4. Arachidonic acid metabolites did not seem to be related to the responses induced by contractile agonists or EFS. 5. In the presence of SP, the contractile responses and [3H]-choline outflow evoked by EFS were dose-dependently enhanced. Contractile responses to EFS and [3H]-choline outflow evoked by EFS were enhanced by SP significantly more than by NKA. Both were abolished by atropine or tetrodotoxin. 6. These results suggest that rabbit tracheal epithelium may modulate SP-induced contractions, both direct and indirect, by inactivation of SP. This phenomenon is widespread in mammals. The rabbit may be a useful model to examine airway cholinergic functions.
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PMID:An ubiquitous modulating function of rabbit tracheal epithelium: degradation of tachykinins. 137 1

1. The effects of calcitonin gene-related peptide (CGRP) and other vasoactive mediators of inflammation on blood flow in the synovial vessels and plasma protein extravasation into the knee (femoro-tibial) joint of the pentobarbitone-anaesthetized rat were measured. 2. Changes in synovial blood flow were estimated by 133xenon clearance from the synovial cavity. CGRP (0.1 pmol and 10 pmol) and prostaglandin E1 (PGE1; 3 pmol and 300 pmol) significantly increased clearance from the knee joint measured 5 min after intra-articular injection. Substance P (10 pmol) had no effect on synovial blood flow. 3. Intra-articular perfusion of the rat knee with CGRP at concentrations up to 0.1 mM, or PGE1 at concentrations up to 10 microM, did not increase plasma extravasation into the synovial cavity measured by accumulation of intravenously injected 125I-albumin in the perfusate. 4. Plasma extravasation into the knee was significantly increased by infusion of bradykinin (0.1 microM), 5-hydroxytryptamine (1 microM) and histamine (0.1 mM), compared with the contralateral joints in the same animals which were perfused with Tyrode solution. 5. Perfusion of the knee joint with substance P did not specifically induce 125I-labelled albumin accumulation in the synovial cavity even at doses that had systemic effects as observed by marked plasma extravasation into other tissues. 6. The increase in plasma extravasation induced by histamine (0.1 mM) was potentiated by co-infusion with CGRP (0.1 microM) and PGE1 (3 microM). However the response to a submaximal dose (0.1 microM) of bradykinin, which induced similar plasma extravasation to histamine (0.1 mM), was not increased by co-infusion with CGRP or PGE1.7. These results show that CGRP is a potent vasodilator in the rat knee. CGRP released from sensory nerves may act synergistically with mediators of increased vascular permeability to modify the inflammatory response in this site.
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PMID:Calcitonin gene-related peptide increases blood flow and potentiates plasma protein extravasation in the rat knee joint. 138 Mar 89

This study examined whether intrathecal (i.th.) injection of different 5-hydroxytryptamine (5-HT) receptor agonists modulated the behavioural response to substance P. Given intrathecally, substance P produces a behavioural syndrome consisting of biting of the lower parts of the abdomen and reciprocal hindlimb scratching, which may be indicative of nociceptive stimulation. The number of substance P-induced bites was reduced when counted 5 min after intrathecal injection of 5-HT, p-chloroamphetamine (PCA) which causes release of 5-HT from neuronal terminals, the non-selective 5-HT receptor agonist quipazine, the selective 5-HT1 receptor agonists (+)-8-hydroxy-2-(di-n-propylamino)tetralin [(+)-8-OH-DPAT], 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969) and 1(m-chlorophenyl)piperazine (mCPP), but was unchanged by treatment with the 5-HT2/5-HT1C receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The number of scratches was significantly increased 5 min after injection of 5-HT and RU 24969. The results showed that intrathecal injection of 5-HT agonists, with a high affinity for the 5-HT1 receptor subtypes, reduced the total number of responses induced by intrathecal injection of substance P, whereas a 5-HT2/5-HT1C receptor agonist did not affect the behavioural response to the intrathecal injection of substance P.
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PMID:Stimulation of 5-HT1 receptors in the spinal cord changes substance P-induced behaviour. 138 63

Immunohistochemical reactions for 12 putative neuromessengers combined with retrograde labeling of phrenic motoneurons identified seven neuromessengers (5-hydroxytryptamine, substance P, thyrotropin-releasing hormone, methionine enkephalin, cholecystokinin, galanin, neuropeptide Y) located within terminal varicosities in the phrenic nucleus. The degree of terminal labeling in the phrenic nucleus varied depending on the peptide. Substance P, thyrotropin-releasing hormone and methionine enkephalin were each tested for colocalization with 5-hydroxytryptamine within terminal varicosities in the phrenic nucleus, and the coincidence of double-labeling varied for each peptide. These results indicate that phrenic motoneurons are subject to modulation by many peptide neuromessengers that may alter their responsiveness to primary excitatory and inhibitory inputs.
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PMID:Multiple putative neuromessenger inputs to the phrenic nucleus in rat. 138 55

1. The effects of L-NG-nitroarginine (L-NOARG) and L-NG-nitroarginine methyl ester (L-NAME) on vasodilatation induced by ATP, substance P, 5-hydroxytryptamine (5-HT), bradykinin and sodium nitroprusside (SNP) were examined in the guinea-pig coronary bed, by use of a Langendorff technique. The effects of these inhibitors of nitric oxide synthesis were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2. The vasodilator responses evoked by low doses of 5-HT (5 x 10(-10)-10(-8) mol) were almost abolished by L-NAME and L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M), although L-NOARG (3 x 10(-5) M) was significantly less potent than L-NAME (3 x 10(-5) M) as an inhibitor of vasodilator responses to 5-HT (5 x 10(-8) mol). 3. The vasodilator responses evoked by substance P (5 x 10(-12)-5 x 10(-9) mol) were reduced in the presence of L-NAME and L-NOARG (both at 10(-5) and 3 x 10(-5) M). The response to substance P was almost abolished by L-NAME and L-NOARG (both at 10(-4) M). 4. The amplitude of the vasodilator responses to ATP (5 x 10(-11) and 5 x 10(-9)-5 x 10(-7) mol) was little affected by either L-NAME or L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M).7. It is concluded that in the guinea-pig coronary vasculature, the vasodilatation evoked by substance P and low doses of 5-HT is mediated almost exclusively via nitric oxide, whereas the vasodilatations evoked by ATP and bradykinin appear to involve other mechanisms in addition to the release of nitric oxide. L-NAME was a more effective agent than L-NOARG in inhibiting the vasodilator actions of 5-HT and ATP in this preparation.
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PMID:Effects of nitric oxide synthase inhibitors, L-NG-nitroarginine and L-NG-nitroarginine methyl ester, on responses to vasodilators of the guinea-pig coronary vasculature. 138 16


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