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 study the esophagus of Podarcis hispanica through different methods to clarify the structure and affinities of its wall innervation. The acetylcholinesterase method reveals cholinesterase activity in two submucosal nervous plexuses, with an increasing degree of structural complexity in the reptilian esophagus, compared with amphibians. Noradrenergic innervation, detected through fluorescence induced by formol, widely spreads its network in both the myenteric and submucosal plexuses (around the blood vessels in the external submucosal plexus, and to the glandular lamina propria in the inner submucosal plexus). Immunohistochemistry for vasoactive intestinal peptide shows a widespread innervation, with neurons clustered in ganglia and also scattered through the VIPergic network, only at the myenteric plexus. Immunohistochemistry for substance P shows a rich innervation along the entire wall of the esophagus, more concentrated in its caudal region, around the blood vessels. Electron microscopy shows the enteric neuronal ultrastructure and its relationship with the esophagus wall.
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PMID:Intrinsic innervation of a reptilian esophagus (Podarcis hispanica). 956 83

The effect of dimethyl sulfoxide (DMSO) on the slow ventral root potential, which is related to nociceptive transmission, was investigated in the isolated spinal cord of a newborn rat. DMSO at 0.3-1% (v/v) enhanced the slow ventral root potential, but not mono- and polysynaptic reflex discharges. DMSO at 1% also enhanced the depolarization induced by substance P or capsaicin. In the presence of tetrodotoxin (0.3 microM), DMSO at 1% did not influence the substance P-induced depolarization but enhanced the acetylcholine-induced depolarization. Edrophonium at 10 microM also enhanced the slow ventral root potential, and the magnitude of the effect was comparable to that of 1% DMSO. In the presence of atropine (0.3 microM) and hexamethonium (30 microM), the effect of edrophonium disappeared, but half of the effect of DMSO remained. Artificial cerebrospinal fluid containing either 0.87% (w/v) urea or 4.6% (w/v) sucrose, which has the same osmotic pressure as that containing 1% DMSO, did not have the same effect as DMSO on the slow ventral root potential. In the saphenous nerve-dorsal root preparation, the compound action potential was enhanced by 4-aminopyridine (10 microM), but was not affected by DMSO up to 3%. The results suggest that DMSO enhances the slow ventral root potential through mechanisms based on the inhibition of cholinesterase activity and other action(s) involved in increasing transmitter release from nerve endings in nociceptive transmission pathways in the isolated spinal cord of the newborn rat. Neither the blockade of K+ channels nor hyperosmotic effects are likely mechanisms of DMSO action.
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PMID:Enhancing effect of dimethyl sulfoxide on nociceptive transmission in isolated spinal cord of newborn rat. 968

1. Although peptides are important modulators of synapses, their action on synapse-glia interactions remain unclear. The amphibian neuromuscular junction (NMJ) was used to examine the effects of substance P (SP) on perisynaptic Schwann cells (PSCs), glial cells at the frog NMJ, by monitoring changes in intracellular Ca2+. 2. SP induced Ca2+ responses that were mimicked by the neurokinin 1 receptor (NK-1) agonist septide and with a shorter delay by the SP fragment, SP(6-11). SP and SP(6-11) responses were blocked by NK-1 antagonists SR140333 and LY303870. 3. Ca2+ responses remained unchanged when extracellular Ca2+ was removed but were blocked after pertussis toxin (PTX) treatment, indicating that the receptors were linked to internal stores of Ca2+ via a PTX-sensitive G-protein. 4. The slowly hydrolysable NK-1 agonist [Sar9, Met(O2)11]-SP only induced Ca2+ responses when applied for a long period of time and not during brief, local applications, suggesting the involvement of SP hydrolysis. Acetylcholinesterase (AChE) may not be involved in SP degradation since Ca2+ responses evoked by SP were unchanged in the presence of the cholinesterase inhibitor neostigmine. 5. Ca2+ responses induced by muscarine and nerve stimulations were almost abolished when preceded by SP applications, while those induced by ATP were significantly reduced. The rundown of the nerve-evoked Ca2+ responses in PSCs was attenuated in the presence of SR140333. 6. These results indicate that endogenous SP is involved in the regulation of PSC activity and that SP is an important modulator of glial cell Ca2+ signalling and synapse-glia communication.
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PMID:Endogenous peptidergic modulation of perisynaptic Schwann cells at the frog neuromuscular junction. 972 29

A circular and a longitudinal muscle strip were prepared from adjacent parts of a guinea-pig ileum and a direct pharmacological comparison made under identical conditions. The longitudinal preparation was sensitive to acetylcholine, methacholine, carbachol, 5-hydroxytryptamine, histamine and nicotine, while the circular preparation was insensitive to 5-hydroxytryptamine, histamine and nicotine, and responded to the choline esters only in high concentrations. Incubation of the preparations with the anticholinesterase, mipafox (NN-diisopropylphosphodiamidic fluoride), sensitized both preparations to the action of acetylcholine; potentiation of the contraction of the longitudinal muscle was 16-times; that of the circular one 4,000-times. The longitudinal muscle was more sensitive than the circular muscle to acetylcholine whether both were treated with mipafox or not. Bradykinin and substance P both stimulated the longitudinal but not the circular muscle, an effect not modified after mipafox. Hyoscine antagonized the responses of the circular muscle strip, treated with mipafox, to acetylcholine and to histamine, but on the longitudinal muscle strip the response to histamine was not affected, the response to acetylcholine being competitively antagonized. Morphine, in the same concentrations on both circular and longitudinal muscle strips, antagonized the stimulant actions of nicotine and to a lesser extent of 5-hydroxytryptamine, but the responses to histamine on the longitudinal muscle strip were not antagonized by morphine which was in contrast to its action on the circular muscle strip. These observations showed that the main differences in the responses of the circular and longitudinal muscle of the guinea-pig ileum to drugs were in the intrinsic properties of the smooth muscle cells. In addition cholinesterase may protect the circular muscle cells. Finally the circular muscle strip preparation proved to be a useful tool to study the action of drugs on the nervous plexuses of the ileum of the guinea-pig.
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PMID:SOME PHARMACOLOGICAL PROPERTIES OF THE CIRCULAR AND LONGITUDINAL MUSCLE STRIPS FROM THE GUINEA-PIG ISOLATED ILEUM. 1411 Jul 54

Small-diameter sensory nerves innervating the skin are responsive to noxious stimuli, and an injury to these nerves is presumably related to neuropathic pain. Injury-induced neuropathic pain in animals can be produced by laser irradiation, which usually requires concomitant use of photosensitive dyes, known as the photochemical approach. It is not clear whether laser irradiation alone can induce neuropathic pain. In addition, two issues are important to apply these approaches: the relationship between the extent of laser irradiation and the occurrence of neuropathic pain, and the susceptibility of small-diameter sensory nerves in the skin to laser-induced neuropathic pain. To address these issues, we designed a new model of focal neuropathy by applying a diode laser of 532 nm (100 mW) to the sciatic nerve and evaluated small-diameter nerves by quantifying skin innervation and large-diameter nerves by measuring amplitudes of the compound muscle action potential (CMAP). Immediately after laser irradiation, epineurial vessels were occluded due to the formation of thrombi, and the blood flow through these vessels was markedly reduced. On postoperative day (POD) 2, animals developed characteristic manifestations of neuropathic pain, including spontaneous pain behaviors, thermal hyperalgesia, and mechanical allodynia. These phenomena peaked during PODs 7-21, and lasted for 3-6 weeks. The neuropathology at the irradiated site of the sciatic nerve included a focal area of axonal degeneration surrounded by demyelination and endoneurial edema. The extent of damage to large-diameter motor and sensory nerves after laser irradiation was evaluated by nerve conduction studies. On the irradiated sides, amplitudes of the compound muscle action potentials and sensory nerve action potentials (SNAPs) were reduced to 65.0% (P < 0.0001) and 42.5% (P < 0.01) of those on the control sides, respectively. Motor innervation of the neuromuscular junctions (NMJs) on plantar muscles was examined by combined cholinesterase histochemistry and immunohistochemistry. The ratio of innervated NMJs on the operated sides decreased to 76.3% of that on the control side. Skin innervation in the territory of the irradiated sciatic nerves was evaluated by immunohistochemistry with neuronal markers. Among these markers, epidermal nerve densities for protein gene product (PGP) 9.5, calcitonin gene-related peptide (CGRP), and substance P (SP) were significantly lower on the irradiated sides than the control sides with a different degree of loss for each marker (42.1-53.1%, P < 0.05). Results suggest that laser-induced focal neuropathy provides a new system for studying neuropathic pain. With this approach, the extent of nerve injury can be quantified. Both small-diameter epidermal nerves and large-diameter sensory and motor nerves are susceptible to laser-induced injury of different degrees.
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PMID:Skin denervation, neuropathology, and neuropathic pain in a laser-induced focal neuropathy. 1564 95

Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.
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PMID:Current and Future Issues in the Development of Spinal Agents for the Management of Pain. 2686 70

The development of metacercariae of Diplostomum pseudospathaceum Niewiadomska, 1984 is accompanied by profound morphological transformations often characterized as metamorphosis, which makes these metacercariae an interesting case for studying the morphogenesis of the digenean nervous system. Although the nervous system of D. pseudospathaceum is one of the most extensively studied among digeneans, there are still gaps in our knowledge regarding the distribution patterns of some neuroactive substances, most notably neuropeptides. The present study addresses these gaps by studying pre-infective metacercariae of D. pseudospathaceum using immunochemical staining and confocal microscopy to characterize the distribution patterns of serotonin (5-HT) and two major groups of flatworm neuropeptides, FMRFamide-related (FaRPs) and substance P-related (SP) peptides. The general morphology of the nervous system was examined with antibodies to alpha-tubulin. The nervous system of the metacercariae was shown to conform to the most common morphology of the nervous system in the hermaphroditic generation, with three pairs of posterior nerve cords and four pairs of anterior nerves. The patterns of FaRP- and 5-HT immunoreactivity (IR) were similar to those revealed in earlier studies by cholinesterase activity, which is in accordance with the known role of these neurotransmitters in controlling muscle activity in flatworms. The SP-IR nervous system was significantly different and consisted of mostly bipolar cells presumably acting as mechanoreceptors. The architecture of the nervous system in D. pseudospathaceum metacercariae is discussed in comparison to that in cercariae of D. pseudospathaceum and metacercariae of related digenean species.
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PMID:Architecture of the nervous system in metacercariae of Diplostomum pseudospathaceum Niewiadomska, 1984 (Digenea). 3072 79


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