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)

In muscularis mucosae from the opossum distal colon, both tone and spontaneous contractions were highly dependent on the available oxygen. Acetylcholine and histamine caused, respectively, atropine- and pyrilamine-sensitive contractions. Norepinephrine relaxed the tissue, an effect abolished by propranolol. Under these conditions norepinephrine failed to elicit contractions and at higher concentrations again caused relaxations. The tissue gave concentration-dependent relaxations to ATP but not to ADP, AMP, or adenosine. Electrical field stimulation (20-30 Hz, 1-2 ms, 120 mA) revealed a cholinergic excitatory innervation and a nonadrenergic, noncholinergic neural inhibition. Cholecystokinin, gastrin, substance P, and vasoactive intestinal polypeptide were without effect on this tissue. In these respects, colonic muscularis mucosae differs considerably from that of other gastrointestinal viscera.
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PMID:Pharmacological characterization of opossum distal colonic muscularis mucosae in vitro. 394 17

The responsiveness (grams per millimeter squared) and sensitivity (pD2 value) of various agonists were examined in isolated stored human bronchial and pulmonary arterial and venous preparations. In isolated bronchial muscles, large preparations (internal diameter about 6 mm) were less responsive (grams per millimeter squared) to contractile agents than smaller preparations (internal diameter approximately 2 mm). Noncumulative concentration-effect curves were produced in bronchial preparations using histamine, acetylcholine, carbachol and barium chloride. Histamine contracted both bronchial and vascular preparations whereas 5-hydroxytryptamine contracted only vascular tissues. The latter effect was always blocked by either methysergide or ketanserin. 5-hydroxytryptamine relaxed bronchial tissues that were contracted with either histamine, acetylcholine or prostaglandin E2. This relaxation was not antagonized by methysergide, ketanserin, propranolol or indomethacin. Dimaprit and 4-methyl histamine were without effect in isolated contracted bronchial preparations. Vasoactive intestinal peptide, Substance P and platelet-activating factor when added to preparations at resting tone failed to induce a contraction. These agents did not relax histamine-contracted isolated human pulmonary muscle preparations. Anti-immunoglobulin E antibody sometimes contracted isolated human bronchial muscle but not pulmonary vascular preparations. However, these data were difficult to assess because of the variations observed. Anti-immunoglobulin G antibody was inactive. Noradrenaline did not elicit a physiological response in isolated bronchial muscle preparations at concentrations which always induced a contraction in the pulmonary vascular preparations. In the presence of propranolol, noradrenaline neither contracted nor relaxed isolated human bronchial preparations. We also determined the sensitivity of isolated bronchial muscle preparations to isoproterenol, salbutamol and theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response and sensitivity of isolated human pulmonary muscle preparations to pharmacological agents. 398 55

The release of dynorphin-(1-17), somatostatin and substance P into the venous effluate of the isolated and vascularly perfused guinea-pig small intestine was measured during rest and peristaltic activity. The peptides were determined by specific radioimmunoassays. Increasing the intraluminal pressure by 5 mbar increased the release of dynorphin-(1-17), somatostatin and substance P. A substantial increase in the release of substance P was only seen in the presence of naloxone (1.5 microM) indicating an inhibitory influence of opioid peptide-containing neurones on the release of substance P. The pressure-induced release of substance P and dynorphin-(1-17) was completely prevented by tetrodotoxin (1.3 microM), which suggests a neural origin of these two peptides. The pressure-induced release of somatostatin was only partially inhibited by tetrodotoxin (1.3 microM) suggesting that somatostatin may also be released from non-neuronal sources, i.e. endocrine mucosal cells. Dimethylphenylpiperazinium (32 microM) increased the release of somatostatin and substance P and this effect was inhibited by tetrodotoxin (1.3 microM). Cholecystokinin-octapeptide (38 nM) induced a large increase in the release of somatostatin but only a minute increase in the release of substance P; these effects of cholecystokinin-octapeptide were not blocked by tetrodotoxin (1.3 microM). Noradrenaline (59 microM) inhibited the pressure-induced release of substance P but not that induced by dimethylphenylpiperazinium (32 microM). Neither the pressure-induced nor the dimethylphenylpiperazinium-evoked release of somatostatin was significantly diminished by noradrenaline. These results indicate that dynorphin-(1-17), somatostatin and substance P may be transmitters involved in the coordination of the peristaltic reflex. Part of the inhibitory effects of opioid peptides and noradrenaline on intestinal motility may be brought about by inhibition of the release of substance P.
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PMID:Release of dynorphin, somatostatin and substance P from the vascularly perfused small intestine of the guinea-pig during peristalsis. 608 15

Two cell culture systems were used for studies of neural functions in vitro. A neuronal hybrid cell line (neuroblastoma x glioma hybrid cells) and primary glial-rich cultures of newborn murine brain. The level of cyclic AMP in both systems is regulated by two groups of hormones, those that stimulate and those that inhibit formation of cyclic AMP. Among the inhibitory hormones active on the hybrid cells are opioids. Therefore the cells are being used in the elucidation of action of opioids. The list of stimulating and inhibitory hormones regulating the primary glial-rich cultures includes several peptide hormones such as the gastrointestinal peptides secretin and vasoactive intestinal peptide, the calcaemic hormones parathyrin and calcitonin, adrenocorticotropin and melanotropins, and somatostatin. Noradrenaline (via alpha- and beta-adrenergic receptors) and adenosine (via A1 and A2 receptors) inhibit and stimulate cyclic AMP synthesis in the primary glial-rich cultures. Bradykinin slowly hyperpolarizes the hybrid cells and elicits formation of cyclic GMP. Both responses desensitize rapidly. Substance P increases the permeability of hybrid cells for Na+, as measured by using 14C-guanidinium as substitute for Na+. Hybrid cells actively accumulate taurine, an amino acid that appears to fulfill important functions in the nervous system. The transport of taurine across the plasma membrane is highly specific for and strictly dependent on Na+. The pumped station hypothesis of taurine action in the nervous system views taurine gradient plus taurine carrier as a transport system for the elimination of sodium from neurons during phases of high neuronal activity.
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PMID:Cell culture as models for studying neural functions. 608 74

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
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PMID:Senile dementia of the Alzheimer type. 613 75

Electrical field stimulation of the isolated pig bladder neck preparation initiated rapid non-adrenergic, non-cholinergic nerve-mediated relaxations. A wide range of substances were examined as possible candidates for the neurotransmitter involved. Of these, only 5-hydroxytryptamine, vasoactive intestinal polypeptide, adenosine and adenosine 5'-triphosphate produced relaxations. Noradrenaline, acetylcholine, substance P, bradykinin and angiotensin II caused contraction, while neurotensin, somatostatin, bombesin and gamma-amino butyric acid were without effect. The nerve response was not blocked by methysergide, ketanserin, chymotrypsin, apamin or 8-phenyltheophylline, although methysergide antagonised the responses to 5-hydroxytryptamine, chymotrypsin blocked the responses to VIP, and 8-phenyltheophylline antagonised the responses to adenosine and ATP.
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PMID:A novel non-adrenergic, non-cholinergic nerve-mediated relaxation of the pig bladder neck: an examination of possible neurotransmitter candidates. 614 1

In isolated detrusor from guinea-pigs and rats substance P (SP) induced concentration-dependent phasic contractions. Rabbit detrusor strips responded to SP with an initial phasic and an ensuing tonic contraction. The concentration-response curve to SP in this preparation had a biphasic appearance. Eledoisin (E) caused contractile responses similar to those of SP when tested on the guinea-pig detrusor. Somatostatin was tested on the rabbit urinary bladder; it caused a concentration-dependent rise in basal tone, but no phasic contraction. The responses to SP and E were not affected by tetrodotoxin or physostigmine. They were only partly inhibited by high concentrations of atropine and the anticholinergic drug PR 197. Noradrenaline and isoprenaline caused a concentration-dependent inhibition of the peptide induced responses in guinea-pig bladder; at high concentrations in the amines this inhibition was almost complete. Indomethacin did not affect the SP induced contractions in the guinea-pig bladder, reduced the responses in the rabbit detrusor, but increased them in the rat bladder. Contractions elicited by SP and E were rapidly diminished or abolished after 30 min. treatment in a calcium-free medium. The responses were also inhibited by the calcium antagonist nifedipine. In guinea-pig preparations depolarized by potassium (127 mM) both SP and E caused a contractile response approximately 20% of that obtained in normal Tyrode solution. It is concluded that SP and E cause contraction of detrusor by a direct effect on the smooth muscle cells, and that this response is dependent on the extracellular calcium concentration. Prostaglandins may be involved in the SP-induced response of the rabbit detrusor.
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PMID:Contractile effects of some polypeptides on the isolated urinary bladder of guinea-pig, rabbit, and rat. 617 55

1. The effect of substance P on the phasic longitudinal contractions of the isolated rabbit ileum has been investigated. The contractions were recorded isotonically. Substance P in concentrations below those which cause tonic contraction (0.2-2 nM) increased the height of the phasic contractions in a concentration-dependent fashion without affecting their frequency (8-12/min).2. The effect of substance P was inhibited by verapamil, ouabain, noradrenaline, and isoprenaline, but was unaffected by tetrodotoxin, atropine, D-2-ala,5-metenkephalin, somatostatin, and vasoactive intestinal polypeptide.3. Tetraethylammonium, which blocks voltage-dependent K(+) channels, enhanced the phasic contractile activity of the rabbit ileum in a manner quite similar to substance P, but the maximal response to tetraethylammonium was larger than that to substance P.4. The effect of matched concentrations of substance P and tetraethylammonium, which enhanced the phasic contractions to a similar extent, was investigated at various concentrations of K(+), Na(+), Ca(2+) and Cl(-) in the bathing medium. Both substance P and tetraethylammonium lost their ability to enhance the phasic contractions when K(+) was omitted from the medium or when its concentration therein was increased by a factor of 4, or when the NaCl concentration was reduced to less than 10%. The relative increase in phasic contractile activity evoked by substance P was smaller than that evoked by tetraethylammonium when more than 90% of the Cl(-) was replaced with propionate.5. Noradrenaline, in a concentration which just abolished the spontaneous phasic contractions (200-300 nM), reduced the enhancing effect of substance P on the phasic activity by 40-50%, but did not influence the effect of tetraethylammonium.6. These results indicate that substance P enhances the phasic longitudinal contractions of the isolated rabbit ileum by a direct action on the smooth muscle cells and that this effect is brought about by facilitation of the myogenically controlled action potential discharges in the ileum. Circumstantial evidence suggests that the underlying ionic mechanism of action of substance P is a decrease in K(+) and Cl(-) conductances.
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PMID:An enquiry into the mechanism by which substance P facilitates the phasic longitudinal contractions of the rabbit ileum. 618 Jan 64

In order to investigate the actions of acetylcholine (ACh), catecholamines and substance P on K transport in the submaxillary gland, measurements of net K flux to and from the gland tissue using flame photometry, Na efflux from the tissue using radioactive 22Na, and membrane potential and input resistance using micro-electrodes were carried out on isolated superfused segments of rat and mouse submaxillary glands. ACh (5.5 X 10(-8) to 5.5 X 10(-4) M), phenylephrine (5 X 10(-7) to 5 X 10(-4) M) or substance P (10(-9) to 10(-5) M) stimulation for 5 min induced a transient K release followed by a small K uptake after the cessation of stimulation. The K release was markedly enhanced by the simultaneous addition of ouabain (10(-3) M). On the other hand, isoprenaline (2.5 X 10(-9) to 2.5 X 10(-5) M) induced a transient K uptake without any preceding K release. The K uptake was completely blocked by the addition of ouabain. Noradrenaline induced only K uptake at a low concentration (3 X 10(-7) M), but induced transient K release followed by marked K uptake at higher concentrations (3 X 10(-6) to 3 X 10(-4) M). The K release induced by noradrenaline was suppressed by the addition of phentolamine (10(-5) M), while the K uptake was suppressed by propranolol (5 X 10(-6) M). The K release induced by ACh, phenylephrine, noradrenaline or substance P was severely reduced by Ca omission from the superfusing solution and restored by the re-admission of Ca. The isoprenaline- or noradrenaline-induced K uptake was, however, little affected by Ca omission. Application of isoprenaline (2.5 X 10(-6) M) induced an increase in 22 Na efflux. The increase in 22Na efflux was completely abolished in the presence of ouabain. Local application to the tissue bath of isoprenaline (4.7 X 10(-13) to 4.7 X 10(-12) mole) or noradrenaline (5.7 X 10(-12) to 5.7 X 10(-11) mole) in the presence of phentolamine (10(-5) M) induced membrane hyperpolarization without any appreciable change in input resistance. The hyperpolarization was abolished in the presence of ouabain (10(-3) M) or propranolol (5 X 10(-6) M) or in a K-free or low Na solution. Higher doses of both agonists, however, induced depolarization or biphasic responses (initial depolarization followed by hyperpolarization). The depolarizations were accompanied by a moderate reduction in input resistance. It is concluded that in the rat and mouse submaxillary gland acinar cells cholinergic, alpha-adrenergic or substance P stimulation causes K release (and perhaps Na uptake) resulting in activation of the Na-K pump, while beta-adrenergic receptor stimulation might directly activate the Na-K pump resulting in K uptake, or might cause Na uptake resulting in activation of the Na-K pump.
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PMID:Activation of potassium transport induced by secretagogues in superfused submaxillary gland segments of rat and mouse. 619 88

The contractile effect of substance P on the longitudinal muscle of the isolated guinea-pig small intestine and the desensitization of the muscle which occurs on prolonged exposure to the peptide have been investigated. All experiments were performed in the presence of atropine. The response to a substance P concentration which produced a nearly maximal effect was not sustained but faded rapidly. It was found that not elimination of substance P from the bath, but desensitization of the muscle to substance P was the main cause for the fading of contraction. Desensitization of the muscle to substance P only developed if the muscle was exposed to the peptide for a certain time. The degree of and the time needed for recovery from desensitization were directly related to concentration of substance P and contact time. Tetraethylammonium (3 mM), which reduces the membrane conductance for K+, enhanced the potency of substance P in contracting the muscle and reduced the fading of contraction. Noradrenaline (295 nM), which increases the K+ conductance, produced opposite effects. Lowering the extracellular Ca2+ concentration to one-tenth decreased the potency of substance P in contracting the muscle, accelerated the fading of contraction, and reduced the ability of the muscle to respond to a second addition of substance P after the response to the first addition had faded away. Concentrations of substance P (22 nM) and tetraethylammonium (30 mM), which produced nearly maximal contractions, slightly enhanced the efflux of 86Rb from pre-loaded muscle strips. Both substances, however, caused a sustained reduction of 86Rb efflux from strips depolarized by high [K+], the effect of substance P being smaller than that of tetraethylammonium. The effect of substance P and tetraethylammonium on 86Rb efflux appeared independent of the extracellular [Ca2+]. On exposure of the muscle to substance P (22 nM) for 8 min the intracellular uptake of 45Ca was first decreased and then increased while the 45Ca influx was instantly enhanced by tetraethylammonium (30 mM) or K+ (108 mM). The delayed increase in 45Ca influx caused by substance P was also observed in muscle strips depolarized with high [K+].(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the mechanism of contraction and desensitization induced by substance P in the intestinal muscle of the guinea-pig. 619 32


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