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)

Neuroactive peptides, including the enkephalins (Met- and Leu-enkephalin; ME, LE) and substance P (SP) are known to be present in the mammalian carotid body, an arterial chemoreceptor organ sensitive to the O2, CO2 and pH levels in blood. The principal parenchymal (type I) cells of the organ, which receive sensory innervation from the carotid sinus nerve (CSN), have been shown to contain both ME and SP; SP is also present in CSN afferent fibers. In the present study, rabbits were exposed in a chamber to a physiological chemoreceptor stimulus (5% O2 in N2) for one hour, then anesthetized during surgical removal of both carotid bodies for later RIA measurement of ME and SP levels in the tissue; control animals were exposed to air in the chamber, but otherwise treated as the hypoxic animals. Both ME and SP levels were significantly reduced (approximately 40%) in the carotid bodies from hypoxic rabbits, compared to their normoxic controls. The results suggest that these neuroactive peptides are released from carotid body elements during physiological stimulation, and consequently may play a role in the transduction of chemosensory information between the type I cells and their apposed afferent terminals.
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PMID:Physiological chemoreceptor stimulation decreases enkephalin and substance P in the carotid body. 243 86

Experiments were performed on 17 anesthetized, paralyzed, and artificially ventilated cats to evaluate the importance of substance P-like peptide (SP) on the carotid body responses to CO2. Single or paucifiber carotid chemoreceptor activity was recorded from the peripheral end of the cut carotid sinus nerve. In eight of the cats the influence of SP on hyperoxic hypercapnic responses was studied. While the animals breathed 100% O2, intracarotid infusion of SP (1 microgram.kg-1.min-1, 3 min) increased chemoreceptor activity by +4.8 +/- 0.3 impulses/s. After SP infusion, inhalation of CO2 in O2 caused a rapid increase in activity that reached a peak and then adapted to a lower level, whereas similar levels of CO2 before SP caused only a gradual increase in carotid body discharge rate without any overshoot in response. Furthermore SP significantly increased the magnitude and slope of the CO2 response. In the other nine cats the effect of intracarotid infusion of an SP antagonist, [D-Pro2,D-Trp7,9] SP (10-15 micrograms.kg-1.min-1), on carotid body responses to 1) hyperoxic hypercapnia (7% CO2-93% O2), 2) isocapnic hypoxia (11% O2-89% N2), and 3) hypoxic hypercapnia (11% O2-7% CO2-82% N2) was examined. SP antagonist had no effect on carotid body response to hyperoxic hypercapnia but significantly attenuated the chemoreceptor excitation caused by isocapnic hypoxia and hypoxic hypercapnia. These results suggest that 1) SP may play an important role in carotid body responses to hypoxia but not to CO2, and 2) the mechanisms of stimulation of the carotid body by hypercapnia and by hypoxia differ.
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PMID:Role of substance P in hypercapnic excitation of carotid chemoreceptors. 244 16

Previous studies suggest that structures within 1 mm of the ventral surface of the medulla (VMS) are involved in the regulation of airway resistance. Furthermore, neurons containing tachykinin peptides have been observed near the surface of the VMS. In the present work, we examined the effects of mammalian tachykinins, substance P (SP) and neurokinin A (NKA), applied locally to the intermediate area of the VMS of cats on tracheal tone and phrenic nerve activity. Since neutral endopeptidase (enkephalinase) has been shown to degrade tachykinin peptides in other tissues, we also investigated the effect of the neutral endopeptidase (NEP) inhibitors (thiorphan and phosphoramidon) on airway tone and phrenic nerve responses to tachykinins when the animals were ventilated with 100% O2 and during hyperoxic hypercapnia and isocapnic hypoxia. Experiments were performed in chloralose-anesthetized cats hyperventilated to phrenic neural apnea or so that the end tidal CO2 was just above the apneic threshold. Trachealis smooth muscle tension was assessed by measuring changes in pressure in a balloon placed in a bypassed segment of trachea (Ptseg). Application to the VMS of SP (10(-5)-10(-3) M) significantly increased tracheal muscle tension. Similar effects were found with applications of NKA. In addition, thiorphan and phosphoramidon potentiated the effects of tachykinins and the responses to hypercapnia and hypoxia of tracheal tone and phrenic nerve activity. Pretreatment with atropine (1 mg/kg) blocked tracheal but not phrenic responses to tachykinins. These suggest that (1) tachykinins acting on structures located on the VMS can increase cholinergic outflow to the airways and augment respiratory motor output, and (2) NEP may be one important modulator of tachykinin-induced effects.
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PMID:Central modulatory effects of tachykinin peptides on airway tone. 248 64

We tested the hypothesis that tachykinins mediate hyperpnea-induced bronchoconstriction (HIB) in 28 guinea pigs. Stimulus-response curves to increasing minute ventilation with dry gas were generated in animals depleted of tachykinins by capsaicin pretreatment and in animals pretreated with phosphoramidon, a neutral metalloendopeptidase inhibitor. Sixteen anesthetized guinea pigs received capsaicin (50 mg/kg sc) after aminophylline (10 mg/kg ip) and terbutaline (0.1 mg/kg sc). An additional 12 animals received saline (1 ml sc) instead of capsaicin. One week later, all animals were anesthetized, given propranolol (1 mg/kg iv), and mechanically ventilated (6 ml/kg, 60 breaths/min, 50% O2 in air fully water saturated). Phosphoramidon (0.5 mg iv) was administered to five of the noncapsaicin-treated guinea pigs. Eucapnic dry gas (95% O2-5% CO2) hyperpnea "challenges" were performed by increasing the tidal volume (2-6 ml) and frequency (150 breaths/min) for 5 min. Capsaicin-pretreated animals showed marked attenuation in HIB, with a rightward shift of the stimulus-response curve compared with controls; the estimated tidal volume required to elicit a twofold increase in respiratory system resistance (ES200) was 5.0 ml for capsaicin-pretreated animals vs. 3.7 ml for controls (P less than 0.03). Phosphoramidon-treated animals were more reactive to dry gas hyperpnea compared with control (ES200 = 2.6 ml; P less than 0.0001). Methacholine dose-response curves (10(-11) to 10(-7) mol iv) obtained at the conclusion of the experiments were similar among capsaicin, phosphoramidon, and control groups. These findings implicate tachykinin release as an important mechanism of HIB in guinea pigs.
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PMID:Tachykinins mediate bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs. 249 85

We investigated the effect of a neuropeptide, substance P, on the electrical and ion transport properties of dog trachea. Posterior mucosal tissues were mounted in Ussing chambers and bathed with Krebs-Henseleit solution, pH 7.4, at 37 degrees C. The solution was gassed with 95% O2, 5% CO2. Substance P (10(-7)M) added to the mucosal bath elicited within seconds a rapid rise in short circuit current with a peak response of 23 microA.cm-2 and an increase in tissue conductance of 0.63 mS.cm-2 (p less than 0.001, n = 20). In 6 experiments, 36Cl and 22Na fluxes were measured under short circuit conditions and they revealed that net Cl secretion increased from 1.46 +/- 0.41 to 2.30 +/- 0.74 mueq.cm-2 X h-1 (mean +/- SE, p less than 0.05). This increase was brought about by enhancement of unidirectional submucosa to lumen flux. Net Na absorption of 0.63 +/- 0.09 did not change significantly (0.49 +/- 0.16). Short circuit current response to substance P was not modified by prior tissue incubation with atropine, phenoxybenzamine, propranolol, or naloxone. Removal of mucosal bath calcium and the presence of calcium channel blocker verapamil did not abolish tissue response to substance P. These findings suggest that nerve fibers containing substance P may play a role in regulation of ion transport across the trachea. This action does not appear to be related to the cholinergic, adrenergic, or oplate receptors.
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PMID:Substance P stimulation of chloride secretion by canine tracheal mucosa. 257 65

The effects of beta-endorphin, vasoactive intestinal polypeptide (VIP) and cholecystokinin octapeptide (CCK-8) on carotid chemoreceptor activity have been investigated in cats anaesthetized with pentobarbitone. Spontaneous chemoreceptor discharge was decreased by intracarotid injection of beta-endorphin and by low doses of VIP, whereas it was increased by CCK-8 and higher doses of VIP, these effects being relatively long-lasting and often associated with changes in systemic blood pressure. The chemoexcitation evoked by acetylcholine and sodium cyanide was reduced during intracarotid infusion of any of the three peptides studied, and that caused by CO2-saturated Locke solution was reduced by beta-endorphin, largely unaltered by VIP and variably affected by CCK-8. The inhibitory effect of beta-endorphin was greatly reduced by naloxone, implying that it probably involved actions at naloxone-sensitive opiate receptors in the carotid body. Substance P was unable to overcome the chemoinhibitory effect of methionine enkephalin. Possible functions of polypeptides in the carotid body are discussed.
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PMID:Effects of beta-endorphin, vasoactive intestinal polypeptide and cholecystokinin octapeptide on cat carotid chemoreceptor activity. 616 57

Infusion of substance P into the renal artery was previously shown to cause a significant natriuresis which was associated with increased kallikrein excretion. Since the renal kinin and prostaglandin (PG) systems may be interrelated, the present study was performed to investigate the effects of substance P on renal function and its potential interaction with the renal PG system in the conscious rat. 24 female Sprague-Dawley rats were infused intravenously with substance P (1 ng . min-1 . kg-1 body weight) and the body weight was kept constant by an intravenous infusion of 0.45% saline. Substance P had no effects on arterial blood pressure, glomerular filtration rate (GFR) and 125I-hippuran clearance in the absence or presence of indomethacin (INDO). Basal UPGE2 V was unaltered by substance P infusion but was suppressed by INDO before and during substance P by 80 and 88%, respectively. Substance P raised urinary flow rate (V) by 105%, CH2O by 96%, UNaV by 378%, UKV by 48% and UPO4V by 147% (p less than 0.001). Although INDO significantly suppressed V, CH2O, and UNaV during all collection periods, it did not affect absolute UPO4V and UKV and the relative rise in V, CH2O, and UNaV induced by substance P. Thus, the diuretic and natriuretic effects of substance P are not mediated by renal PG, but are partially blunted by INDO through increased distal absorption of sodium and water, INDO has no effect on substance P-induced alterations in proximal tubular function.
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PMID:Substance P-induced changes in kidney function in the conscious rat: relation to the renal prostaglandin system. 618 93

Neuropharmacological mechanisms in central regulation of respiration in anesthetized rats were studied in a whole body plethysmographic model. Neurotransmitter agonists and antagonists were administered intracerebroventricularly or locally into the brain and the respiratory pattern was analysed. The four anesthetics: enflurance (E), halothane (H), pentobarbital sodium (P) and urethane (U) were found to have different effects on central respiratory regulation. Respiratory frequency was higher after H and U compared to after E and P. Animals anesthetized with H exhibited a lower inspiratory drive and a slightly depressed sensitivity to CO2. The responses to the neuropeptides substance P and TRH as well as the amino acid neurotransmitter GABA were partly modified after the different forms of anesthesia. Apomorphine (i.c.v) induced a biphasic, haloperidol reversible, respiratory response in H- and U- (but not in E- and P-) anesthetized rats. The initial bradypnoic response might be due to a decreased sensitivity to afferent vagal signals, while the following tachypnoic phase might be elicited by dopaminergic mechanisms at posterior diencephalic and upper midbrain levels (hypoxic, hypercapnic tachypnea). The tachypnoic response was inhibited by a graded exposure to CO2. The effects of different neurotransmitters were further analysed in H-anesthetized animals. GABA and the GABA agonist muscimol exerted a depressant effect on ventilation in contrast to the GABA-like drugs GHBA an baclofen. Exogenous GABA depressed all respiratory parameters studied exept for inspiratory time and was found to affect mainly respiratory timing mechanisms. An increase in endogenous GABA levels induced by the GABA transaminase inhibitor AOAA blunted the respiratory response to CO2 and induced a ventilatory depression similar to that seen after exogenous GABA. A significance correlation between brain stem GABA levels and respiratory duty cycle was found. The tripeptide TRH induced a marked tachypnea due to the extrahypothalamic actions of the peptide. A delay in the response was seen after local injection into the nucleus tractus solitarius and the tachypnea was abolished by CO2 exposure. The ventilatory effects might be elicited by mechanisms similar to those involved in the tachypnoic response to apomorphine. The tachypnea was potentiated by GABA (possibly due to that both agents act on inspiratory off-switch lowering mechanism) and by methylatropine or naloxone (possibly due to secondary pertubation by cholinergic or enkephalinergic mechanisms). A stimulation of ventilation (increase in tidal volume) was seen after substance P (SP) due to an increase in inspiratory drive and o
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PMID:Neuropharmacological aspects of central respiratory regulation. An experimental study in the rat. 620 94

During the inflammatory response, tissues release histamine (H), substance P, serotonin (5-HT), prostaglandins and kinins, agents that mediate manifestations of inflammation such as pain, vasodilation, increased capillary permeability and smooth muscle contraction. In this study we investigated whether racemic (R[+]) ketamine (K) and its isomers are spasmolytic on intestinal smooth muscle contracted by inflammatory mediators, and whether the spasmolytic effect of K is related to changes in calcium influx through the L-type calcium channel or to an interaction of K with opioid receptors. We measured the contractions of guinea-pig ileum mounted in an organ bath containing Tyrode's solution gassed with 95% O2/5% CO2 at 37 degrees C. In the first protocol we determined the effect of K and its isomers on contractions induced by five mediators: 10(-7) M H, 10(-8) M substance P, 10(-8) M neurokinin A, 5 x 10(-9) M bradykinin and 5 x 10(-7) M 5-HT. For each of these mediators, we plotted concentration-response curves for the inhibitory effect of K, and from regression fitting of these curves, we calculated the IC50 concentration of K that inhibited the contraction by 50%). In the second protocol we measured the contraction induced by the calcium ionophore A23187 (5.0 x 10(-6) M), both alone and after 1.8-7.2 x 10(-4) M R(+/-)K. Then we examined how the inhibition caused by R(+/-)K was affected by increases in the concentration of extracellular calcium by adding calcium (1.8-7.2 x 10(-3) M).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ketamine inhibits contractile responses of intestinal smooth muscle by decreasing the influx of calcium through the L-type calcium channel. 748 30

The carotid body is an arterial chemoreceptor organ sensitive to blood levels of O2, CO2 and pH. The present immunocytochemical and neurochemical study has demonstrated the presence of an extensive plexus of nitric oxide (NO)-synthesizing nerve fibers in this organ. These nitric oxide synthase (NOS)-containing axons are closely associated with parenchymal type I cells and with blood vessels in the carotid body. Denervation and retrograde tracing experiments have revealed that these fibers arise from NOS-immunoreactive and nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive neuronal cell bodies located in the petrosal ganglion and the carotid body, and dispersed along the glossopharyngeal and carotid sinus nerves (CSN). Within the petrosal ganglion, these neurons are topographically segregated from the catecholaminergic cells, and they contain the neuropeptide, substance P. NOS-positive autonomic microganglial cells in the carotid body and CSN also exhibit choline acetyltransferase (ChAT) immunoreactivity. Our results suggest that nitric oxide may be a novel neuronal messenger in the mammalian carotid body involved in the modulation of chemosensory transduction and transmission in this organ.
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PMID:Neurons synthesizing nitric oxide innervate the mammalian carotid body. 750 96


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