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)

The in vitro responses of rat urinary bladder, to substance P and capsaicin were studied at 1, 4, 16, and 26 weeks of diabetes induction by streptozotocin. We also studied the role of epithelium in these responses. The results were compared with those obtained in age-matched control rats. The bladder contractile response to exogenous substance P was similar in both groups at all stages (1-26 weeks) studied, whereas the bladder response to capsaicin gradually decreased with the progression of diabetes. Atropine did not inhibit these responses whereas indomethacin slightly reduced substance P- but not capsaicin-induced responses in control and diabetic rats. The removal of epithelium slightly increased the substance P- and capsaicin-induced responses in control tissue; these responses were significantly reduced in tissue excised from diabetic rats. Our results indicate that, in rat urinary bladder, diabetes (1) provokes an impairment of capsaicin-sensitive sensory fibers but not of the cholinergic system even at an early stage (4 weeks) of the disease, (2) has no effect on the sensitivity of smooth muscle cells to substance P, (3) stimulates the release of epithelial contracting factors, partially non-prostanoic. Furthermore epithelium removal impairs acetylcholine-induced contraction in bladder excised from diabetic rats but not in controls.
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PMID:Effect of substance P and capsaicin on urinary bladder of diabetic rats and the role of the epithelium. 753 29

We studied the mechanisms involved in the airway smooth muscle (ASM) contraction to substance P (SP) in normal (control) and allergen-sensitized (immune) rabbits as well as immune rabbits exposed to allergen via the airways (immune challenged). Cumulative concentration-response curves to SP (1 x 10(-9) to 1 x 10(-4) M) were performed in ASM segments in the absence and presence of atropine (10(-5) M) in vitro. The maximal contractile response (g tension/g tissue) at 10(-4) M SP and ASM contractions at various concentrations of SP were expressed as means +/- SE. We found no difference in the contractile response to SP between control and immune animals. ASM segments obtained from immune-challenged rabbits were more responsive to SP. Atropine shifted to the right the concentration-response curves and decreased the maximal ASM contraction at 10(-4) M SP in all three groups; this effect, however, was greater in immune-challenged tissues. These findings demonstrate an increased contractile response to SP in immune-challenged animals mediated by a more pronounced facilitation of cholinergic neurotransmission. We conclude that the final ASM response to SP is the result of a complex interaction between direct effects on ASM and indirect effects through modulation of cholinergic neurotransmission.
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PMID:SP-induced contraction of airway smooth muscle in normal and allergen-sensitized rabbits: mechanism of action. 753 96

Distension of rat rectal colon causes electrogenic Cl- secretion via the plexus submucosus Meissner. This study aimed to identify the neurotransmitter(s) of this reflex pathway. Distension was applied to partially stripped rat rectal colon in Ussing chambers. Baseline short-circuit current (Isc) increased and then slowly declined again within 30 min. The increase in Isc 10 min after distension (delta Isc10) was 1.8 +/- 0.3 mumol.h-1.cm-2. Atropine (1 microM) did not alter delta Isc10. Thus cholinergic neurons with muscarinic synapses were not involved. Tissues were then desensitized to vasoactive intestinal peptide (VIP) or substance P. This required continuous infusion of VIP or substance P into the chamber; otherwise, desensitization was only temporary due to rapid degradation of VIP or substance P. During substance P desensitization, distension still induced a secretory response (delta Isc10 not significant vs. control), whereas during VIP desensitization distension no longer had an effect. Furthermore, a polyclonal anti-VIP antiserum blocked 81% and the VIP antagonist [p-Cl-D-Phe6,Leu17]VIP blocked 89% of the distension-induced delta Isc10, supporting the results of the desensitization experiments. To localize the site of VIP action, tetrodotoxin (TTX) was used. The TTX effect on Isc during VIP stimulation was not different from its effect on baseline Isc. This is in accord with the concept that the VIP receptors are mainly located on the enterocytes. We conclude that VIP, but not substance P or acetylcholine (via muscarinic receptors), acts as a neurotransmitter in the distension-induced reflex pathway, causing Cl- secretion in rat rectal colon.
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PMID:Distension-induced electrogenic Cl- secretion is mediated via VIP-ergic neurons in rat rectal colon. 753 19

The in vitro responses of longitudinal preparations of rat stomach fundus and ileum to capsaicin at 1, 8, 4, 16 and 26 weeks and to substance P at 1 and 8 weeks from diabetes induction were studied. The results were compared with those obtained in age-matched control rats. The contractile responses to exogenous substance P and capsaicin were not affected in the stomach fundus from diabetic rats. Atropine (1 microM) did not antagonize the substance P-induced response whereas it inhibited about 90% of the capsaicin-induced response in controls and about 60% of the response in diabetic rats. At the resting tone, capsaicin induced a relaxation followed by a contraction in stomach fundus of control rats. Only a contraction was evoked in diabetic rats. In carbachol (0.05-0.1 microM) pre-stimulated strips, a complete restoration of the biphasic response was obtained in the diabetic state. The contractile response elicited by exogenous substance P was not significantly increased in the ileum preparations from diabetic rats; nevertheless the EC50 value for substance P was reduced 8 weeks after the onset of diabetes. The response elicited by capsaicin in the ileum of control rats was also biphasic. The capsaicin-induced contraction was greater in tissue from diabetic rats as compared with controls and relaxation was not evident. An age-related decrease of the contraction was also evident in both groups. Atropine (1 microM) partially antagonized the responses to substance P and capsaicin. The inhibition of the responses with atropine was more evident in control than in diabetic rats. These results suggest that the myogenic actions of several agonists in these two tissues are differently modified in experimental diabetes.
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PMID:Effect of substance P and capsaicin on stomach fundus and ileum of streptozotocin-diabetic rats. 754 Jan 41

The mechanisms underlying cigarette smoke-induced bronchoconstriction were studied by using selective blockade of muscarinic acetylcholine receptors, neurokinin receptors and production of eicosanoids of the cyclooxygenase pathway in anesthetized guinea pigs. Inhalation of three breaths of cigarette smoke (University of Kentucky research series 2R1; 2.45 mg of nicotine and 35.3 mg of tar per cigarette) reproducibly induced an immediate bronchoconstriction; total pulmonary resistance increased from 0.24 +/- 0.02 to 1.44 +/- 0.21 cmH2O.ml-1.s (P < 0.01) and dynamic lung compliance decreased from 0.53 +/- 0.03 to 0.39 +/- 0.06 ml/cmH2O (P < 0.05) in 10-15 breaths after the smoke inhalation. Atropine pretreatment (50 micrograms/kg i.v.) prevented the immediate decrease in dynamic lung compliance and reduced the immediate increase in total pulmonary resistance by approximately 55%. The atropine-resistant bronchoconstriction occurring immediately after smoke inhalation was completely blocked by a pretreatment with a combination of CP-99994 (0.3 mg/kg i.v.) and SR-489668 (0.3 mg/kg i.v.), the antagonists of neurokinin-1 and neurokinin-2 receptors, respectively. However, a delayed and sustained bronchoconstriction still persisted and reached a plateau in 45-55 breaths after smoke inhalation challenge. This delayed response was completely prevented by pretreatment with indomethacin (5 mg/kg i.v.). We conclude that the smoke-induced bronchoconstriction in guinea pigs consists of an early phase induced by both a cholinergic reflex and tachykinin release, probably evoked by the activation of bronchopulmonary C fibers, and a late phase caused by the action of arachidonic acid metabolite(s) of the cyclooxygenase pathway.
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PMID:Cigarette smoke-induced bronchoconstriction: cholinergic mechanisms, tachykinins, and cyclooxygenase products. 766 27

The ascending reflex contraction of intestinal circular muscle involves both cholinergic and tachykininergic transmission, which are thought to be activated by different degrees of distension. Substance P, however, is colocalized with acetylcholine in myenteric neurons, and the present study examined the role of these transmitter substances in relation to low- and high-degree distension and with regard to ascending propagation of excitation. Reflex contractions in segments of the guinea pig isolated small intestine were evoked by inflation of an intraluminal balloon and recorded orally to the site of distension. Atropine (12.5 nM), hexamethonium (3 microM) and the neurokinin (NK)2-selective tachykinin antagonist MEN 10,376 (10 microM) inhibited contractions induced by low-degree distension to a larger extent than contractions induced by high-degree distension, whereas the receptor-nonselective tachykinin antagonist spantide (30 microM) did not differentiate in this way. Atropine, hexamethonium and spantide also depressed the propagation of excitation, i.e., the response recorded 2 cm away from the distension site was inhibited to a larger degree than the response recorded 1 cm away from the distension site. In contrast, MEN 10,376 did not interfere with the ascending propagation of excitation, and the NK1-selective tachykinin antagonist GR 82,334 (10 microM) was without effect on the ascending reflex contraction. These observations show that tachykinins and acetylcholine comediate ascending reflex contractions triggered by both low- and high-degree distension. When seen in context with the known projection of myenteric neurons, the findings relating to the ascending propagation of excitation indicate that NK2 receptors participate in neuromuscular transmission only, whereas neuroneuronal transmission involves both nicotinic and muscarinic acetylcholine receptors.
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PMID:Ascending enteric reflex contraction: roles of acetylcholine and tachykinins in relation to distension and propagation of excitation. 767 49

1. Gastric blood flow and motor responses to greater splanchnic nerve stimulation and intra-arterial injection of tachykinins were studied in anaesthetized dogs. 2. Splanchnic nerve stimulation (40 V, 10 Hz) with pulse durations of 0.05 and 1 msec caused a gastric relaxation and contraction, respectively. Both types of stimulation produced a decrease followed by an increase in blood flow. The responses to stimulation with a pulse duration of 0.05 msec were inhibited by hexamethonium. 3. After treatment with hexamethonium, stimulation with 1 msec caused frequency-dependent gastric contraction and vasodilation. Both responses had two components, sensitive and resistant to atropine. 4. Intra-arterial injection of substance P (SP), neurokinin A (NKA), neurokinin B (NKB), physalaemin (PHY) or eledoisin (ELE) elicited dose-dependent gastric contraction and vasodilation. The order of potency for contraction was SP = PHY = ELE = NKA >> NKB and that for vasodilation was SP = PHY > ELE > NKA > NKB. 5. Atropine partly inhibited the tachykinin-induced gastric contraction but not gastric vasodilation. Spantide partly inhibited the atropine-resistant vasodilation but not contraction in response to splanchnic nerve stimulation and SP. 6. It is concluded that splanchnic nerve stimulation produced cholinergic and SPergic vasodilation after ganglionic blockade in the dog stomach.
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PMID:Gastric vasodilator and motor responses to splanchnic stimulation and tachykinins in the dog. 768 99

Neurokinin A (NKA), substance P (SP), and neurokinin B (NKB) enhanced the contractile force of uterine preparations from estrogen-treated rats. Neurokinin A was more and NKB less potent than SP. The actions of SP were enhanced by phosphoramidon (1 microM) but were unaffected by captopril (10 microM) or bestatin (10 microM). The actions of the peptides were enhanced in the combined presence of phosphoramidon, captopril, and bestatin; the potency order remained NKA > SP > NKB. Atropine inhibited responses to NKB but not to NKA, and slightly reduced those to SP. Specific binding of [125I]-iodohistidyl-neurokinin A (INKA) to uterine membranes was displaced by the tachykinins with a potency order of NKA > SP > NKB. These findings indicate that in the rat uterus 1) tachykinins act at an NK-2 receptor, and that another tachykinin receptor on cholinergic nerves may also be present; and 2) endopeptidase-24.11 participates in the inactivation of the tachykinins.
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PMID:Mammalian tachykinins stimulate rat uterus by activating NK-2 receptors. 768 98

Changes in pulmonary endothelial permeability and in microvascular hemodynamics in response to cumulative concentrations of acetylcholine (ACh) (10(-8) M to 10(-5) M) were investigated in isolated, perfused rabbit lungs. The total pressure gradient was partitioned into four components: arterial, pre- and postcapillary and venous. The capillary filtration coefficient (Kf, c) also was evaluated. ACh caused a significant increase in arterial and precapillary pressures at concentrations higher than 3 x 10(-6) M. The total pressure gradient and precapillary were significantly increased whereas arterial, postcapillary and venous pressure gradient remained unchanged. In papaverine (3 x 10(-4) M)-pretreated lungs, the vasoconstriction was abolished and a concentration-dependent increase in Kf,c was recorded from 10(-8) to 10(-5) M ACh. This reaction was accompanied by pulmonary edema. Atropine, indomethacin, aspirin, ketanserin, clonidine, morphine and (+/-)-CP 96-345, an antagonist of neurokinin NK1 receptors, completely prevented the effects of ACh on Kf,c. In contrast, cromolyn sodium and SR48968, a neurokinin NK2 antagonist, did not inhibit the response to ACh. Terfenadine together with cimetidine had a partially inhibitory effect. Changes in the Kf, c similar to those observed with ACh were induced by capsaicin (10(-4) M) by exogenous substance P (10(-7) M) and by 5-hydroxytryptamine (5-HT) (10(-4) M). The effects of SP were inhibited by aspirin, (+/-)-CP 96,345 and ketanserin, but not by atropine and antihistaminics. 5-HT effects were prevented by aspirin and not by (+/-)-CP 96,345. It was concluded that ACh-induced pulmonary edema was due to an increase in the capillary filtration coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of neuropeptides in acetylcholine-induced edema in isolated and perfused rabbit lungs. 768 2

1. Neuromuscular transmission in the circular muscle of the canine proximal colon was examined, in the presence and absence of nitric oxide synthase inhibitors, by use of mechanical and intracellular microelectrode recording techniques. 2. Electrical field stimulation (EFS; 0.1-20 HZ) produced frequency-dependent contractions of circular muscle strips which reached a maximum at 15 Hz. These responses were enhanced by NG-monomethyl-L-arginine (L-NMMA; 300 microM) and reduced by atropine (1 microM). The effects of L-NMMA were reversed by L-arginine (3 mM). All responses to EFS were abolished by tetrodotoxin (1 microM). 3. In the presence of atropine, phentolamine and propranolol (all at 1 microM; 'non-adrenergic, non-cholingergic (NANC) conditions'), EFS evoked frequency-dependent inhibition of phasic contractions which reached a maximum at 5 Hz. At higher frequencies of EFS, inhibition diminished, and these responses were followed by post-stimulus excitation. 4. Under NANC conditions and in the presence of L-NG-nitroarginine methyl ester (L-NAME; 200 microM), EFS evoked contractions at frequencies of 5 Hz or greater. These contractions were reduced by co-incubation with L-arginine (2 mM) and abolished by tetrodotoxin (1 microM). 5. In the presence of atropine (1 microM), EFS (5-20 Hz) caused frequency-dependent inhibition of electrical slow waves. In the presence of L-NAME (100 microM) and atropine, the inhibitory response to EFS was abolished and an increase in slow wave duration was seen at stimulation frequencies greater than 5 Hz. The effects of EFS on slow wave duration were abolished by tetrodotoxin (1 microM). 6. Atropine-resistant contractions to EFS were enhanced by indomethacin (10 microM) and reduced or abolished by the non-selective NK1/NK2 tachykinin receptor antagonist D-Pro2, D-Trp7,9 SP, and by the selective NK2 receptor antagonist MEN 10,376 (10 microM).7. Exogenous tachykinins mimicked non-cholinergic excitatory electrical and mechanical responses. The rank order of potency for contraction was neurokinin A>neurokinin B>substance P, suggesting a predominance of the NK2 sub-type of tachykinin receptors on colonic smooth muscle cells. Low concentrations of neurokinin A also increased the amplitude and duration of electrical slow waves.8. These results suggest that: (i) in previous studies, non-cholinergic excitatory responses were masked by the simultaneous release of NO; (ii) non-cholinergic excitatory responses occur throughout the period of stimulation and are not manifest only as 'rebound' excitation; (iii) one or more tachykinins, possibly,acting via NK2 receptors, may mediate non-cholinergic excitatory responses.
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PMID:Inhibition of nitric oxide synthesis reveals non-cholinergic excitatory neurotransmission in the canine proximal colon. 768 1


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