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)

1. Rapid change of bath temperature from 37 degrees C to 27 degrees C and vice versa caused longitudinal contraction of the isolated guinea-pig ileum. 2. Tetrodotoxin, tropicamide, noradrenaline, isoprenaline, morphine, and the met-enkephalin analogue FK 33-824 depressed the responses or accelerated the fade of the contraction induced by rapid cooling when added after the response had reached its maximum. 3. Hexamethonium had no influence on the responses. 4. Physostigmine potentiated all responses and reversed the fade of contraction induced by rapid cooling when added after this contraction had reached its maximum. 5. The effects of rapid cooling or warming were not altered in preparations made tachyphylactic to substance P; the response to rapid warming, but not cooling, was partially inhibited under tachyphylaxis to 5-hydroxytryptamine. 6. Antazoline, phentolamine, naloxone, and indomethacin did not block the responses. 7. Capsaicin firt potentiated and subsequently depressed the responses to both rapid cooling and warming. 8. The results indicate that rapid change of bath temperature induces longitudinal contraction by excitation of postganglionic cholinergic fibres.
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PMID:Longitudinal contraction of isolated guinea-pig ileum induced by rapid cooling. 9 5

Bronchospasm induced by i.v. injection of equieffective doses of acetylcholine, capsaicin or selective tachykinin receptor agonists ([Sar9]SP sulfone or [beta-Ala8]neurokinin A (NKA-4-10)) (for NK1 and NK2 receptors, respectively) was studied in anaesthetized guinea-pigs. The NK1 and NK2 receptor antagonists, (+/-)-CP96,345 (3 mumol/kg i.v.) and MEN 10,376 (3 mumol/kg i.v.), selectively abolished the bronchoconstriction induced by the respective agonist, showing that both NK1 and NK2 receptors mediate bronchoconstriction in guinea-pig airways and that they are activated independently. Capsaicin-induced bronchospasm was inhibited by atropine (1.5 mumol/kg i.v.) and MEN 10,376 (3 mumol/kg i.v.), but unaffected by (+/-)-CP96,345 (3 mumol/kg i.v.). Hexamethonium (79 mumol/kg i.v.), propranolol (17 mumol/kg i.v.) and physostigmine (0.9 mumol/kg i.v.) enhanced the airway constriction induced by acetylcholine, capsaicin, [Sar9]SP sulfone or [beta-Ala8]NKA-(4-10) while guanethidine (67 mumol/kg s.c. for two days) increased only bronchoconstriction induced by capsaicin or the selective NK2 receptor agonist. In hexamethonium-treated animals, MEN 10,376 still abolished the increase in insufflation pressure induced by [beta-Ala8]NKA-(4-10) and reduced the increase elicited by capsaicin. In summary, in anaesthetized guinea pig i.v. capsaicin-induced bronchospasm through activation of postjunctional NK2 (but not NK1) receptors along with activation of cholinergic pathways. This motor response is moderated by the simultaneous stimulation of a sympathetic bronchodilating mechanism(s), possibly through activation of NK2 receptors localized in sympathetic ganglia.
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PMID:Effects of selective tachykinin receptor antagonists on capsaicin- and tachykinin-induced bronchospasm in anaesthetized guinea-pigs. 135 35

Electrical stimulation of the right vagus nerve causes a biphasic contraction of the guinea pig isolated right bronchus. The "first-phase" is blocked by hexamethonium or atropine and the "second-phase" is eliminated by capsaicin pretreatment. We investigated a potential interaction between capsaicin-sensitive nerves and cholinergic nerves in the guinea pig bronchus. Hexamethonium (100 microM) abolished the first-phase contraction but had no effect on the capsaicin-sensitive second-phase contraction. In the presence of hexamethonium, atropine (0.1 microM) significantly decreased the amplitude of the second-phase contraction by 28%. Similar results were observed with the M3-selective muscarinic receptor antagonist, 4-diphenyl-acetoxy-M-methylpipe-radine, but not with the M2 muscarinic antagonist, AFDX-116. Atropine also reduced contractions induced by exogenously applied neurokinin A. We then analyzed the effect of stimulating capsaicin-sensitive fibers with electrical field stimulation on vagus nerve evoked cholinergic contractions. By reducing the stimulus intensity we were able to evoke vagus nerve-mediated contractions that were exclusively cholinergic in nature. The cholinergic contractions were significantly increased after stimulation of capsaicin-sensitive fibers by about 50%. By contrast, contractions elicited by exogenous methacholine were unaffected after field stimulation of capsaicin-sensitive responses. Our findings indicate that the contractions of the guinea pig bronchus elicited by stimulation of capsaicin-sensitive nerves are due in part to muscarinic cholinergic receptor activation. Secondly, our data demonstrate that the cholinergic contractions elicited by vagal preganglionic nerve stimulation are potentiated by neurotransmitter(s) released from capsaicin-sensitive fibers in bronchus.
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PMID:Functional interactions between capsaicin-sensitive and cholinergic nerves in the guinea pig bronchus. 171 77

Junction potentials were recorded from circular muscle cells of the guinea pig ileum at various sites oral and anal to a transmural stimulus in the presence of atropine, apamin, and substance P antagonism (desensitization) at 30 degrees C. A short train of pulses produced an inhibitory junction potential (slow IJP), which preceded an excitatory junction potential (slow EJP). The slow IJP was observed up to 56.4 +/- 2.9 mm oral and 65.4 +/- 2.2 mm anal to the stimulus. The slow EJP was observed up to 50.4 +/- 1.9 mm oral and 58.3 +/- 2.1 mm anal to the stimulus. Hexamethonium (400 microM) decreased the amplitudes of the slow IJP and slow EJP at all sites. After hexamethonium, the slow IJP was observed up to 37.3 +/- 2.3 mm oral and 39.8 +/- 2.1 mm anal to the stimulus and the slow EJP was 44.2 +/- 2.5 mm oral and 43.3 +/- 2.6 mm anal to the stimulus. The slow IJP and slow EJP were associated with an increase and decrease in membrane resistance, respectively. Conditioning depolarizations of the circular muscle cells reduced the amplitudes of the slow IJP and slow EJP. Both were abolished at a membrane potential of approximately -25 mV. Conditioning hyperpolarizations increased the amplitude of both the slow IJP and slow EJP. Ionic substitution experiments with low external chloride solution (12.4 mM) resulted in an immediate increase in slow IJP and slow EJP amplitudes, whereas more prolonged perfusion resulted in a significant decrease in slow IJP and slow EJP amplitudes. 4,4'-Diisothiocyanostilbene-2,2'-disulfonic acid (400 microM) resulted in decreases in slow IJP and slow EJP amplitudes. These results suggest that the slow IJP and slow EJP are due to a decrease and increase in membrane chloride conductance, respectively. The noncholinergic neural pathways responsible for the slow IJP and slow EJP extend approximately 40 mm orally and anally along the longitudinal axis of the guinea pig ileum.
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PMID:Chloride-mediated junction potentials in circular muscle of the guinea pig ileum. 171 21

Experiments were performed on chloralosed cats with ligated adrenals. The peripheral ends of the preganglionic sympathetic nerves to the colon were stimulated and colonic motility was monitored by a volumetric method. Electric nerve stimulation with various intensities elicited inhibitory motor responses and occasionally contractions. Hexamethonium and/or guanethidine blocked all inhibitory actions and revealed pure excitatory responses at high stimulation intensities. These colonic contractions were inhibited by atropine. However, atropine-resistant contractions were sometimes observed, predominantly in the colorectal region. Thoracic sympathetic nerves affected the motility in the proximal colon only, while lumbar sympathetic nerves acted on both proximal and distal parts. Strength-duration relationships and sensitivity to local heating suggest that the excitatory responses are due to an antidromic activation of thin, possibly afferent nerve fibres. Small doses of substance P injected close i.a. induced colonic contractions unchanged by hexamethonium and/or guanethidine but sensitive to atropine. The neurally-induced colonic contractions are suggested to be due to an antidromic activation of thin sensory neurons which in the periphery release substance P, in turn activating cholinergic motor neurons, thus constituting an axon reflex arrangement. The possibility of a similar axon reflex mechanism, associated to thin afferents, activating adrenergic inhibitory neurons at the prevertebral ganglionic level is discussed.
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PMID:Non-nicotinic, non-adrenergic excitatory motor fibres in the preganglionic sympathetic supply to the feline colon. An axon reflex arrangement associated to thin sensory neurons, involving substance P? 241 74

The role of cholinergic neurons in central cardiovascular regulation is not well understood, however, activation of brain cholinergic neurons in several species evokes a hypertensive response. As with central cholinergic stimulation, intracerebroventricular (i.c.v.) injection of substance P (sP) elicits a pressor response in unanesthetized rats. The purpose of this study was to determine whether the cardiovascular effects following i.c.v. injection of this neuropeptide are mediated by central cholinergic neurons. Therefore, the cardiovascular response to sP was examined in control rats, and in animals pretreated centrally with classical pre- and post-synaptic cholinergic antagonists. Drugs were administered directly into the lateral ventricle while rats were freely-moving in their home cages. I.c.v. injection of sP produced a dose - dependent increase in arterial pressure and heart rate. The hypertensive response was significantly reduced by pretreatment with hemicholinium-3. This dose (20 ug) of hemicholinium-3 is capable of producing a maximal depletion of brain acetylcholine levels. The increase in heart rate to substance P was not as sensitive to hemicholinium-3 pretreatment as was blood pressure. Central pretreatment with the nicotinic receptor antagonist, hexamethonium was more effective than the muscarinic antagonist, atropine in blocking the pressor response to sP. Hexamethonium did not significantly alter the tachycardic response to the peptide, but atropine produced a small, but significant reduction in the response. Therefore, the pressor response to central injection of sP may be mediated to a large extent through cholinergic pathways involving nicotinic receptors.
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PMID:Cholinergic neurons and the cardiovascular response produced by central injection of substance P in the normotensive rat. 242 34

A preparation of isolated small intestine from the guinea-pig was studied in which reflex responses of the circular muscle were recorded intracellularly when sensory receptors in the mucosa were stimulated mechanically. This preparation was used to examine the properties of mucosa to muscle reflexes that involve non-cholinergic motor neurons innervating the circular muscle. Reproducible stimulation of the mucosa was achieved by stroking with a motor-driven brush. Gentle brush-strokes applied to the mucosa typically evoked inhibitory junction potentials anal to the stimulus and excitatory junction potentials at recording sites oral to the stimulus. Both events were rapid in onset and up to 25 mV in amplitude. The reflexes were blocked by tetrodotoxin (0.5 microM). Junction potentials declined in amplitude with distance from the stimulus, the amplitude of the excitation 15 mm oral to the stimulus was half that at 5 mm from the stimulus, whereas the amplitude of the inhibitory potential at 40-45 mm was about 60% of that at 5-10 mm anal to the stimulus. Hexamethonium (100-200 microM) blocked the ascending excitation but only slightly reduced the descending inhibition. Ascending excitation was blocked by antagonists for substance P receptors in the muscle, and inhibition was substantially reduced by apamin (0.2 microM), both before and after hexamethonium. Both responses were abolished by removal of the mucosa from the stimulus site and when lesions were made through the myenteric plexus between the stimulation and recording sites, but persisted when similar lesions were made through the submucous plexus. It is concluded that there are neurons with mechanoreceptive nerve endings in the mucosa. Stimulation of such sensory neurons leads to activation of pathways in the myenteric plexus that excite motor neurons to the muscle both oral and anal to the stimulation site. The demonstration that mucosa to muscle reflexes can be consistently evoked in the small intestine in vitro provides an opportunity for close analysis of the reflex pathways. Such analysis is not so readily achieved when reflexes are initiated by distension that, by moving the intestine, can dislodge the recording electrode.
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PMID:Reflex changes in circular muscle activity elicited by stroking the mucosa: an electrophysiological analysis in the isolated guinea-pig ileum. 246 86

Using an electromyographic technique, an ascending excitatory response was recorded "in vitro" in the presence of atropine in the cat small intestine up to 70 mm orally with respect to the site of repetitive transmural nerve stimulation. This non-cholinergic ascending excitatory response was characterized by an increase in the slow wave amplitude and spiking activity. This response was reversibly abolished by Tetrodotoxin (3,1 X 10(-6) M) but remained unchanged after exposure of the intestine to: Hexamethonium (4,9 X 10(-6) M) plus Tubocurarine (1,4 X 10(-5) M), Guanethidine (5 X 10(-7) to 5 X 10(-5) M), Domperidone (2,3 X 10(-7) to 2,3 X 10(-5) M), Naloxone (3 X 10(-7) to 3 X 10(-5) M), Methysergide (2,8 X 10(-7) to 2,8 X 10(-5) M), Metergoline (2,4 X 10(-5) M), Methiotepin (2,1 X 10(-5) M) and Mepyramine (2,3 X 10(-5) M). This response was unaffected by the substance P analogues, D-Pro2, D-Phe7, D-Trp9-Substance P (10(-5) M) or D-Pro2, D-Trp7-9-Substance P (10(-5) M) but was reversibly abolished after exposure of the intestine to substance P (10(-6) M). Moreover substance P still effectively abolished this response in the presence of any two of the above analogues. The results of the present study show that the non-cholinergic excitatory response elicited in the cat small intestine due to the activity of long ascending pathways probably involved substance P. The functional significance of this response is discussed.
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PMID:Non-cholinergic ascending excitatory response in the cat small intestine: possible involvement of substance P. 246 25

We studied the effects of close intra-arterial injections of substance P on colonic motor activity in the conscious state, during anesthesia, and during acute laparotomy. In the conscious state, with enteric nerves intact, substance P stimulated postsynaptic cholinergic neurons to induce a large amplitude and long duration contraction. This response was blocked by prior close intra-arterial injection of atropine and tetrodotoxin (TTX) but not hexamethonium. Hexamethonium and TTX given alone, close intra-arterially, induced a series of short-duration contractions. Prior close intra-arterial administration of hexamethonium significantly enhanced the colonic motor response to substance P. After blockade of nerve conduction by TTX, substance P induced a series of short-duration contractions with characteristics different from those when the nerves were functioning. Anesthesia alone had little effect on the colonic motor response to substance P, but laparotomy inhibited it significantly. Laparotomy similarly inhibited the contractile response to bethanechol. Gut handling had no further effect on this inhibition. We conclude that in the conscious state substance P acts preferentially on postsynaptic cholinergic neurons to contract colonic circular muscle. When the intrinsic nerves are blocked, substance P may act directly on the smooth muscle to induce circular muscle contractions with characteristics different from those induced when nerves are intact. Substance P also has a weak inhibitory motor effect by its action on presynaptic neurons that synapse on postganglionic intrinsic inhibitory neurons. Anesthetic doses of barbiturates have no major effects on the neuromuscular response to substance P, but laparotomy significantly inhibits the smooth muscle response and selectively blocks some neurons.
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PMID:Local effect of substance P on colonic motor activity in different experimental states. 247 74

The release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) from the strips of guinea-pig ileum was investigated in the presence of neurotensin. Neurotensin evoked the release of [3H]-GABA from the strips preloaded with [3H]-GABA, and the evoked release was Ca2+-dependent and tetrodotoxin-sensitive. Hexamethonium, scopolamine, [D-Pro2,D-Trp7,9] substance P and pretreatment with substance P did not alter the neurotensin-evoked release of [3H]-GABA. Pretreatment with neurotensin inhibited the release of [3H]-GABA evoked by neurotensin but not by high K+, thereby indicating that neurotensin induced a specific desensitization of its own receptor. These observations indicate that neurotensin may stimulate the GABAergic neurone through its own receptor. Neurotensin evoked the release of [3H]-ACh from strips preloaded with [3H]-choline and this release was Ca2+-dependent and tetrodotoxin-sensitive. The evoked release of [3H]-ACh was not affected by hexamethonium, scopolamine and [D-Pro2,D-Trp7,9] substance P. Bicuculline partly inhibited the neurotensin-evoked release of [3H]-ACh; thus neurotensin seems to induce a release of ACh partly through the release of endogenous GABA. All this evidence indicates that neurotensin induces release of GABA as well as ACh from the myenteric neurones of the guinea-pig ileum.
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PMID:Release of gamma-aminobutyric acid and acetylcholine by neurotensin in guinea-pig ileum. 356 60


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