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)

Simultaneous intracellular recordings were made from pairs of circular muscle (CM) cells, at the oral and anal ends of a segment of guinea-pig distal colon, to investigate the neuronal mechanisms underlying faecal pellet propulsion. When a minimum degree of circumferential stretch was applied to sheet preparations of colon, recordings from CM cells revealed either no ongoing junction potentials, or alternatively, small potentials usually < 5 mV in amplitude. Maintained circumferential stretch applied to these preparations evoked an ongoing discharge of excitatory junction potentials (EJPs) at the oral recording site (range: 1-25 mV), which lasted for up to 6 h. The onset of each large oral EJP was time-locked with the onset of an inhibitory junction potential (IJP) at an anal recording electrode, located 2 cm from the oral recording. Similar results were obtained in isolated intact tube preparations of colon, when recordings were made immediately oral and anal of an artificial faecal pellet. The amplitudes of many large (> 5 mV) oral EJPs were linearly related to the amplitudes of anal IJPs occurring 20 mm apart. In the absence of an L-type Ca(2+) channel blocker, action potentials occurred on each large oral EJP. Synchronized discharges of stretch-activated EJPs and IJPs were preserved following pretreatment with capsaicin (10 microM), were unaffected by nifedipine (1 microM) and did not require the mucosa or submucous plexus. EJPs and IJPs were abolished by hexamethonium (300 microM) or tetrodotoxin (1 microM), but persisted in the presence of pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10 microM) or an NK(3) tachykinin receptor antagonist (Neurokinin A 4-10; 100 nM to 5 microM). In summary, maintained circumferential stretch of the distal colon activates a population of intrinsic mechanosensory neurons that generate repetitive firing of ascending excitatory and descending inhibitory pathways to CM. These mechanosensory neurons, which may be interneurons, are stretch sensitive, rather than muscle tension sensitive, since they are resistant to muscular paralysis. We suggest the synchrony in onset of oral EJPs and anal IJPs over large regions of colon is due to synchronous synaptic activation of ascending and descending interneurons.
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PMID:A rhythmic motor pattern activated by circumferential stretch in guinea-pig distal colon. 1245 39

ATP has recently emerged as an important proinflammatory mediator that has direct excitatory actions on sensory neurons through activation of ion channel-coupled P2X receptors. The purpose of the current work is to assess whether ATP alters the release of neuropeptides from sensory neurons and the receptors mediating this putative action. Exposing embryonic sensory neurons in culture to concentrations of ATP up to 300 microm did not increase the release of immunoreactive substance P or calcitonin gene-related peptide from sensory neurons. However, pre-exposing sensory neurons to 0.1 to 100 microm ATP prior to and throughout administration of 30 nM capsaicin resulted in a significant augmentation of release evoked by the vanilloid. This sensitizing action of ATP is blocked by suramin but not pyridoxal phosphate-6-azobenzene-2,4-disulfonic acid and is mimicked by the P2Y receptor agonists, 2-2-chloroadenosine triphosphate and UTP, but not by 2-(methylthio)adenosine 5'-triphosphate or alpha,beta-methyleneadenosine 5'-diphosphate. This profile of drug actions suggests that the sensitizing actions of ATP are mediated by P2Y receptors. Pretreating sensory neurons with bisindolylmaleimide I, a selective protein kinase C (PKC) inhibitor, attenuates the augmentation of capsaicin-induced peptide release by ATP, further implicating P2Y receptors in the actions of ATP. Immunoblotting also indicates the presence of P2Y2-like immunoreactive substance in embryonic dorsal root ganglia neurons. Together, these data support the notion that ATP acts at P2Y receptors in sensory neurons in a PKC-dependent manner to augment their sensitivity to other stimuli.
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PMID:ATP augments peptide release from rat sensory neurons in culture through activation of P2Y receptors. 1282 29

Slow excitatory postsynaptic potentials (EPSPs) in enteric neurons arise from diverse sources, but which neurotransmitters mediate specific types of slow EPSPs is unclear. We investigated transmitters and receptors mediating slow EPSPs in myenteric neurons evoked by electrical stimulation of the mucosa in guinea pig small intestine. Segments of ileum or jejunum were dissected to allow access to the myenteric plexus adjacent to intact mucosa, in vitro. AH and S neurons were impaled with conventional intracellular electrodes. Trains of stimuli delivered to the mucosa evoked slow EPSPs in AH neurons that were blocked or depressed by the neurokinin-1 (NK1) tachykinin antagonist SR140333 (100 nM) in 10 of 11 neurons; the NK3 tachykinin receptor antagonist SR142801 (100 nM) had no effect on slow EPSPs in seven of nine AH neurons. Single pulses to the mucosa evoked fast EPSPs and slow depolarizations in S neurons. The depolarizations were divided into intermediate (durations 300-900 ms) or slow (durations 1.3-9 s) EPSPs. The slow EPSPs were blocked by pyridoxal phosphate-6-axophenyl-2-4-disulfonic acid (30 microM, N = 3) or the specific P2Y(1) antagonist MRS 2179 (10 microM, N = 6) and were predominantly in anally projecting S neurons that were immunoreactive for nitric oxide synthase (NOS). In contrast, intermediate EPSPs were predominantly evoked in NOS-negative neurons; these were abolished by MRS 2179 (N = 8). Thus activation of pathways running from the mucosa excites three different types of slow EPSP in myenteric neurons, which are mediated by either a tachykinin (NK1, AH neurons) or a purine nucleotide (P2Y(1), S neurons).
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PMID:Electrical stimulation of the mucosa evokes slow EPSPs mediated by NK1 tachykinin receptors and by P2Y1 purinoceptors in different myenteric neurons. 1940 13

The guinea pig bladder is innervated by at least five distinct major classes of extrinsic sensory neurons. In this study, we have examined the mechanisms of mechanotransduction and chemosensitivity of two classes of bladder afferents that have their endings in the vicinity of the urothelium: stretch-sensitive muscle-mucosal mechanoreceptors and stretch-insensitive, mucosal high-responding afferents. The non-selective P2 purinoreceptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid did not affect stretch- or stroking-induced firing of these afferents but significantly reduced the excitatory action of alpha,beta-methylene ATP. Blocking synaptic transmission in Ca(2+)-free solution did not affect stretch-evoked firing but slightly reduced stretch-induced tension responses. Stroking-induced firing of both classes of afferents was also not affected in Ca(2+)-free solution. Of blockers of mechano-gated channels, benzamil (100 microM), but not amiloride (100 microM), Gd(3+) (100 microM) or SKF 96365 (50 microM), inhibited stretch- and stroking-induced firing. Serotonin (100 microM) applied directly onto receptive fields predominantly activated muscle-mucosal afferents. Muscarine (100 microM) and substance P (100 microM) in 24% and 36% cases activated only mucosal high-responding units. Bradykinin (10 microM), but not prostaglandin E2 (10 microM), excites predominantly mucosal units. High (80 mM) K(+) solution activated both afferent classes, but responses of mucosal units were 4 times greater. In contrast to muscle-mucosal units, most mucosal high-responding units were activated by hot Krebs solution (45-46 degrees C), low pH (pH 4) and capsaicin (3 microm). TRPV1 antagonist, capsazepine (10 microM) was without effect on mechanotransduction by mucosal high-responding afferents. The results show that mechanotransduction of these two types of afferents are not dependant upon Ca(2+)-dependent exocytotic release of mediators, or ATP, and it is likely that benzamil-sensitive stretch-activated ion channels on their endings are involved in direct mechanotransduction. The chemosensitivity to agonists and noxious stimuli differs significantly between these two major classes of bladder afferents that reflects their different physiological and pathophysiological roles in the bladder.
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PMID:Mechanotransduction and chemosensitivity of two major classes of bladder afferents with endings in the vicinity to the urothelium. 1960 32