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 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

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

In order to develop an in vitro model of vascular tissue for pharmacological studies, segments of porcine coronary arteries were incubated in culture media under sterile conditions in cell culture incubator at 37 degrees C with 95% O2 + 5% CO2. After 3 days of incubation, changes in isometric tension were measured in vascular rings and compared with the fresh tissue. KCl (10-75 mM) and prostaglandin F2 alpha (1-20 microM) produced a similar concentration-dependent contraction in the incubated and fresh arteries. The concentration-dependent relaxation curves produced by 2-chloroadenosine (10(-8) to 10(-4) M) and isoproterenol (10(-8) to 10(-5) M) were unaltered in the incubated tissue versus fresh. Similarly, the relaxation responses to forskolin and sodium nitroprusside (10(-8) to 10(-5) M) were unaffected in the incubated arteries. The relaxations produced by substance P (10(-12) to 10(-8) M) and bradykinin (10(-7) M)--the endothelium-dependent agents--were also unaltered in the incubated rings versus fresh. Therefore, we conclude that after the incubation of porcine coronary artery for 3 days, the contraction/relaxation responses to various agonists acting through different mechanisms were unaltered in porcine coronary artery. This in vitro model of vascular smooth muscle provides a potential for pharmacological and toxicological studies.
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PMID:An in vitro pharmacological model of vascular smooth muscle. 750 42

In the present study, we tested the hypothesis that substance P (SP) is an excitatory peptide to the rat carotid body and plays an important role in chemosensory excitation by hypoxia. Chemosensory discharge was recorded from the cut carotid sinus nerve in 19 anaesthetized, paralyzed and mechanically ventilated rats. Intracarotid administration of SP augmented the chemoreceptor activity in a dose-dependent manner. Maximal excitation was seen with 10 nmol SP. Carotid body stimulation by SP was independent of its effects on arterial blood pressure. The effect of SP antagonists, D-Pro2-D-Trp7,9-SP (DPDT-SP) or Spantide, on chemoreceptor responses to SP and hypoxia was examined in 12 rats. Close carotid body administration of either antagonist at doses of 40 micrograms.kg-1.min-1 elicited an augmentation followed by a progressive depression of baseline carotid body activity. SP antagonists significantly reduced peptide-induced carotid body stimulation and also markedly attenuated the chemoreceptor response to hypoxia. Systemic administration of sodium bicarbonate stimulated the carotid bodies, presumably by releasing CO2, and the bicarbonate-induced chemoreceptor stimulation was not affected by SP antagonists. From these results we conclude that in rats (a) SP stimulates the carotid bodies independently of its effects on arterial blood pressure, and (b) SP is associated with the chemosensory stimulation by hypoxia but not with other excitatory stimuli.
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PMID:Tachykinin antagonists in carotid body responses to hypoxia and substance P in the rat. 752 Jan 91

A possible involvement of perivascular vasodilatory neuropeptides in subarachnoid haemorrhage (SAH) has been evaluated in man by measuring the levels of calcitonin gene related peptide (CGRP)-, substance P (SP)- and vasoactive intestinal peptide (VIP)-like immunoreactivity (LI) in the cranial venous outflow and in CSF in 34 patients admitted to the hospital after an acute SAH. After operation with aneurysm clipping and nimodipine treatment, blood samples were taken from the external jugular vein (EJV) or cerebrospinal fluid (CSF) and analysed for neuropeptide levels with specific radioimmuno assays (RIA) during the postoperative course. The degree of vasoconstriction in the patients was monitored with Doppler ultrasound recordings bilaterally from the middle cerebral (MCA) and internal carotid arteries (ICA) following the EJV blood sampling every second day. The mean value of all CGRP-LI measurements in EJV during the entire course of SAH (n = 20) revealed a significantly higher level as compared to controls. The highest CGRP-LI levels were found in patients with the highest velocity index values (vasospasm). The relationship Vmean MCA/Vmean ICA was used as an index of vasoconstriction. In patients with MCA aneurysms (n = 10), a significant correlation (r = 0.65, p < 0.05) was found between the vasospasm index and CGRP-LI levels. There were no changes observed in the SP- and VIP-LI levels. Alterations in cerebrovascular tone induced by changing arterial CO2 tension or lowering of blood pressure (ketanserin infusion test) did not alter the levels of the perivascular peptides in the EJV. In addition, CGRP-, SP-, VIP- and neuropeptide Y (NPY)-LI were analysed in CSF in the post-operative course after subarachnoid haemorrhage (SAH) in 14 patients. The CSF VIP-LI was lower in SAH than in control (p < 0.05). The CGRP-LI level was measurable in SAH CSF but not in CSF of controls. In individual patients with marked vasoconstriction increased levels of CGRP-LI (up to 14 pmol/L) and NPY-LI (up to 232 pmol/L) were observed. The results of this study are in support of our hypothesis that there is an involvement of the sensory peptide CGRP in a dynamic reflex aimed at counterbalancing vasoconstriction in SAH.
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PMID:Alterations in perivascular dilatory neuropeptides (CGRP, SP, VIP) in the external jugular vein and in the cerebrospinal fluid following subarachnoid haemorrhage in man. 753 26

1. The goal of the present study was to identify potential neurotransmitter candidates in the Breuer-Hering (BH) reflex pathway, specifically at synapses between the primary afferents and probable second-order neurones (pump cells) within the nucleus tractus solitarii (NTS). We hypothesized that if activation of specific receptors in the NTS is required for production of the BH reflex, then (1) injection of the receptor agonist(s) would mimic the reflex response (apnoea), (2) injection of appropriate antagonists would impair the apnoea produced by either lung inflation or agonist injection, and (3) second-order neurones in the pathway would be excited by either lung inflation or agonists while antagonists would prevent the response to either. 2. Studies were carried out either in spontaneously breathing or in paralysed, thoracotomized and ventilated rats in which either diaphragm EMG or phrenic nerve activity, expired CO2 concentration and arterial pressure were continuously monitored. The BH reflex was physiologically activated by inflating the lungs. 3. Pressure injections (0.03-15 pmol) of selective excitatory amino acid (EAA) receptor agonists, quisqualic acid (Quis) and N-methyl-D-aspartic acid (NMDA) into an area of the NTS shown previously to contain neurones required for production of the BH reflex produced dose-dependent apnoeas that mimicked the response to lung inflation. Injection of substance P (0.03-4 pmol) did not alter baseline respiratory pattern. 4. Injections of the EAA antagonists, kynurenic acid (Kyn; 0.6-240 pmol), 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the BH region of the NTS reversibly impaired the apnoea produced by lung inflation. All three antagonists reduced or abolished the apnoeas resulting from injection of Quis or NMDA, and slowed baseline respiratory frequency. In contrast, injections of the highly selective NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acids (AP5), in doses sufficient to block the apnoeic response to NMDA, neither altered the reflex apnoea evoked by lung inflation nor the baseline respiratory pattern. 5. Pump cells located within the BH region were excited by pressure injections of the broad spectrum EAA agonist, DL-homocysteic acid (DLH). Kyn reversibly blocked the excitation of pump cells in response to either lung inflation or DLH injection. 6. These findings suggest that EAAs mediate primary afferent excitation of second-order neurones in the Breuer-Hering reflex pathway, primarily through the activation of non-NMDA EAA receptor subtypes.
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PMID:Pulmonary stretch receptor afferents activate excitatory amino acid receptors in the nucleus tractus solitarii in rats. 822 27


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