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 measured the intracellular free calcium ion concentration [( Ca2+]i) of acinar cells in isolated feline tracheal submucosal glands in response to secretagogues using the Ca2(+)-sensitive fluorescent dye fura-2. The secretagogues included cholinergic, adrenergic agonists, substance P (SP), and vasoactive intestinal polypeptide (VIP) which induce mucus glycoprotein secretion from feline tracheal submucosal glands. Methacholine (MCh) produced a significant increase in [Ca2+]i of up to 9.8 times that of control in a dose-dependent fashion at concentrations of 10(-8) to 10(-3) M. [Ca2+]i increase by MCh reached a peak within 30 s after stimulation and thereafter showed a sustained rise. In Ca2(+)-free medium, MCh produced an initial transient rise, which was less than 30% of that in a Ca2(+)-containing solution, and which lasted for 60 s with no prolonged sustained rise in [Ca2+]i. Atropine abolished MCh-evoked [Ca2+]i increase. Phenylephrine and SP produced a prolonged increase in [Ca2+]i without an initial transient increase. Phenylephrine (up to 10(-4) M) evoked an increase in [Ca2+]i by up to 240% that of control, which was abolished by prazosin. SP (up to 10(-4) M) also evoked an increase in [Ca2+]i by 155% that of control, which was abolished by atropine. By contrast, both isoproterenol (up to 10(-5) M) and VIP (up to 10(-5) M) failed to alter [Ca2+]i. These findings indicate that the mucus glycoprotein secretion evoked by muscarinic cholinergic, alpha-adrenergic agonist or SP can be mediated by intracellular Ca2+, whereas that by beta-adrenergic agonists or VIP cannot.
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PMID:Intracellular calcium concentration of acinar cells in feline tracheal submucosal glands. 170 76

Although certain prostaglandins have been found to be inhibitory to nerve-evoked salivary flow, little is known of the effects the leukotrienes on salivary secretion. It was the purpose of this investigation to examine the effects of leukotrienes C4 (LTC4) and D4 (LTD4) on salivary secretion in the rat, using methacholine or substance P to induce basal secretion, and to test whether or not the observed effects of these eicosanoids were receptor-mediated by using the leukotriene receptor blocker FPL-55712. Methacholine (3 x 10(-4) M), or substance P (1 x 10(-6) M) was infused intra-arterially to stimulate secretion and saliva was collected separately from the parotid gland and the submandibular gland of anesthetized rats. LTC4 and LTD4 (each at 1 x 10(-9) to 1 x 10(-6) M) were found to reduce methacholine- and substance P-induced salivary flow in a dose-related manner. Salivary protein concentration and amylase activity were not significantly altered by the leukotrienes; however, arginine-esterase activity, stimulated by substance P, was increased by both leukotrienes. FPL-55712 (1 x 10(-8) M) was shown to reduce the inhibitory effects of LTC4 and LTD4, suggesting the involvement of leukotriene receptors for these agents in their action.
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PMID:The modulatory effects of leukotrienes C4 and D4 on methacholine- and substance P-induced salivary secretion in rats. 245 57

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

The cholinoceptive properties of dorsal horn neurons (lamina III-V) were investigated by means of intracellular recordings from the rat isolated spinal cord slice preparation. In half of the neurons investigated, acetylcholine (ACh) evoked a dose-dependent slow depolarization and increase in excitability; hyperpolarization was observed in 10% of neurons. Acetyl-beta-methylcholine (MCh) similarly depolarized 39% and hyperpolarized 25% of neurons tested; depolarization was also observed following bethanechol. Responses to the muscarinic agonists were abolished by atropine (10(-5) M). Nicotine depolarized 84% of tested neurons; dihydro-beta-erythroidine (5 x 10(-5) M) and (+)-tubocurarine (10(-6) M) antagonized this depolarization. ACh-, MCh- and nicotine-induced depolarizations, associated with changes in input resistance, were maintained in the presence of tetrodotoxin (10(-6) M). Substance P, as well as repetitive electrical stimulation of the dorsal root, also evoked depolarization in ACh-sensitive neurons. Atropine, but not (+)-tubocurarine, diminished responses to both substance P and dorsal root stimulation. These results indicate that dorsal horn neurons are ACh-sensitive and possess both muscarinic and nicotinic receptors. In addition, the parallel sensitivity of neurons to muscarinic agonists, substance P and dorsal root stimulation, as well as the parallel antagonistic effect of atropine, are supportive of a common ionic mechanism underlying the activation of muscarinic and substance P receptors.
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PMID:Cholinergic effects on spinal dorsal horn neurons in vitro: an intracellular study. 260 85

The metabolism of phosphatidate in rat parotid acinar cells was investigated, particularly with regard to the actions of agonists known to act by mobilizing Ca2+. When cells were incubated in medium containing 10 microM-[32P]Pi, phosphatidate was rapidly labelled, approaching an apparent steady-state with a half-time of approx. 20 min. Methacholine provoked a more than doubling of phosphatidate radioactivity, which was reversed by the muscarinic antagonist atropine. These results suggest that phosphatidate labels to near steady-state rapidly and that in cells prelabelled for 60 min the increase in radioactivity induced by agonists probably reflects net synthesis rather than an increase in specific radioactivity. Phosphatidate synthesis in response to methacholine was rapid and occurred, within the resolution of a few seconds, with no measurable latency. Adrenaline and substance P also stimulated phosphatidate synthesis but both agonists were less efficacious than methacholine. A Ca2+ ionophore, ionomycin, did not provoke phosphatidate synthesis. By using a protocol that eliminates the receptor-regulated Ca2+ pool, it was demonstrated that methacholine-induced phosphatidate formation does not come about as a consequence of Ca2+ influx nor of Ca2+ release. These results indicate that the phosphatidate synthesis response has characteristics compatible with its previously suggested role as a primary mediator of membrane Ca2+-gating.
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PMID:Regulation of phosphatidate synthesis by secretagogues in parotid acinar cells. 618 Jul 40

Vasoactive intestinal polypeptide (VIP) and substance P (SP) immunoreactivity are reduced in the cutaneous nerves of diabetic patients with peripheral neuropathy. The functional significance of this finding was studied by measuring the forearm sweat response to intradermal methacholine and the effect of coadministration of VIP and SP in six normal subjects, and in six diabetic patients with neuropathy and eight without. Flare responses to the two peptides were also measured. Methacholine-induced sweat output was significantly greater in neuropathic patients compared with the other groups (p < 0.05), suggesting upper limb denervation supersensitivity. VIP and SP alone did not evoke sweating in any subject. Injection of VIP or SP reduced methacholine-induced sweating to a similar degree in all groups, except that the reduction was smaller in the non-neuropathic group than in the others (p = 0.028 versus normal subjects, p = 0.014 versus neuropathic diabetic patients). Flare responses to the peptides were markedly reduced in the neuropathic patients compared with the other groups (p < 0.01). In neuropathic patients, increased sweat responses and decreased flare coexist with diminished neurophysiological measurements; cutaneous sweating and flare responses provide valuable additional information to conventional methods of neurological assessment in diabetic neuropathy.
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PMID:The effects of vasoactive intestinal polypeptide and substance P on methacholine-induced sweating and vascular flare in diabetic neuropathy. 754 18

The role of platelet-activating factor (PAF) and substance P in stimulating abnormal motor activity during ileal inflammation was investigated in conscious dogs. All test substances were infused close-i.a. in short segments of the ileum. Ileal inflammation was induced by mucosal exposure to a series of ethanol and acetic acid infusions. In the normal state, PAF stimulated phasic contractions and some giant migrating contractions (GMCs), whereas substance P stimulated only phasic contractions. During inflammation, PAF stimulated a significantly greater number of GMCs, but there was no significant difference in the area under phasic contractions between the normal and inflamed states. Atropine, tetrodotoxin, hexamethonium, verapamil, diltiazem, and dantrolene significantly inhibited the response to PAF in both the normal and the inflamed state. By contrast, inhibition of nitric oxide by N omega-nitro-L-arginine methyl ester enhanced the contractile response to PAF. N-(6-ammohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride, a calmodulin antagonist, did not affect the response to PAF. Methacholine, neostigmine and motilin stimulated only phasic contractions during the normal state, but they stimulated both phasic contractions and GMCs during the inflamed state. We conclude that PAF is one of the inflammatory response mediators that may stimulate GMCs during ileal inflammation. The inflammatory response may modulate the enteric neuronal and cellular control of contractions such that the cholinergic mechanisms of stimulation of GMCs are sensitized during inflammation.
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PMID:Platelet-activating factor (PAF) stimulates giant migrating contractions during ileal inflammation. 885 95

Guanosine 3',5'-monophosphate (cGMP) is an intracellular messenger in various kinds of cell. We investigated the regulation of cGMP production by nitric oxide (NO) in rabbit submandibular gland cells. Methacholine, a muscarinic cholinergic agonist, stimulated cGMP production in a dose- and time-dependent manner, but the alpha-agonist phenylephrine, substance P and the beta-agonist isoproterenol failed to evoke cGMP production. In fura-2-loaded cells, methacholine induced an increase in intracellular Ca2+ ([Ca2+]i) in a concentration-dependent manner, which was similar to that for cGMP production. When the external Ca2+ was chelated with EGTA, methacholine failed to induce cGMP production. Ca2+ ionophore A23187 and thapsigargin, which induce the increase in [Ca2+]i without activation of Ca2+-mobilizing receptors, mimicked the effect of methacholine. cGMP production induced by methacholine, A23187 and thapsigargin was clearly inhibited by NG-nitro-L-arginine methylester (L-NAME), a specific inhibitor of nitric oxide synthase (NOS). S-Nitroso-N-acetyl-DL-penicillamine (SNAP), a NO donor, induced cGMP formation. In the lysate of rabbit submandibular gland cells, Ca2+-regulated nitric oxide synthase activity was detected. These findings suggest that cGMP production induced by the activation of muscarinic cholinergic receptors is regulated by NO generation via the increase in [Ca2+]i.
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PMID:Methacholine-induced cGMP production is regulated by nitric oxide generation in rabbit submandibular gland cells. 1212 66

Measures of bronchial responsiveness are widely used for the diagnosis and monitoring of asthma. A vast array of non-specific bronchoconstrictor stimuli is available. Methacholine and histamine cause airflow limitation predominantly through a direct effect on airway smooth muscle. Indirect challenges (adenosine, exercise and hypertonic saline) induce airflow limitation by an action on cells other than smooth muscle cells, with a variety of cells, mediators and receptors being involved in this process. Bronchial responsiveness to a direct stimulus is only weakly related to airway inflammation, whereas indirect airway challenges might better reflect active airway inflammation. Both direct and indirect airway challenges are useful outcome parameters in clinical studies of asthma. For example, an indirect challenge responds to treatment with inhaled steroids within hours to days, whereas improvement in direct responsiveness might take months to years. Bronchial challenges are also an essential step in the development of new anti-asthma treatments, such as adenosine or tachykinin receptor antagonists.
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PMID:Bronchial hyperresponsiveness: too complex to be useful? 1281 Jan 85