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)

A potassium (K+) channel activator, BRL 38227, inhibited goblet cell secretion in guinea-pig trachea induced by either electrical stimulation of the vagus nerves or acute inhalation of cigarette smoke, two stimuli which activate both cholinergic nerves and capsaicin-sensitive sensory nerves. BRL 38227 failed to inhibit methacholine- or substance P-induced goblet cell secretion which suggests that K+ channel activators inhibit neurogenic goblet cell secretion via a prejunctional effect on cholinergic and sensory nerves.
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PMID:K+ channel activator inhibition of neurogenic goblet cell secretion in guinea pig trachea. 138 99

The vascular smooth muscle contractile response to neuropeptide Y (NPY), potassium, noradrenaline, histamine and serotonin was studied in circular segments of isolated vessels in vitro from rabbits with alloxan-induced diabetes mellitus. The injection of alloxan resulted in a marked and maintained increase in serum glucose as early as 1 week after treatment. Four vessel types were examined: abdominal aorta, and renal, left anterior descending coronary and middle cerebral arteries. There was no difference in the contractile response to histamine or serotonin between control and diabetic vessels. However, in the cerebral artery the contractile response to noradrenaline was reduced in the diabetic group, while in the aorta and the renal artery no significant differences were seen. Noradrenaline failed to evoke any contractile response in the coronary arteries in either group. NPY induced strong, concentration-dependent contractions of coronary and cerebral arteries, but did not have any contractile effect per se in aorta or renal arteries, either in control or in alloxan-treated rabbits. The maximal contractile effect and the sensitivity to NPY was significantly less in diabetic coronary and cerebral vessels as compared to control. There was no difference in dilator effect of acetylcholine and substance P between the diabetic animals and the control group in any of the vessel types, indicating that the changed vascular responses to NPY and noradrenaline were not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of NPY and noradrenaline in the peripheral sympathetic nervous system are selectively attenuated in this model of chronic diabetes.
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PMID:Diminished contractile responses to neuropeptide Y of arteries from diabetic rabbits. 158 98

An investigation of the mechanism of peppermint oil action was performed using isolated pharmacological preparations from guinea pig large intestine and patch clamp electrophysiology techniques on rabbit jejunum. Peppermint oil relaxed carbachol-contracted guinea pig taenia coli (IC50, 22.1 micrograms/mL) and inhibited spontaneous activity in the guinea pig colon (IC50, 25.9 micrograms/mL) and rabbit jejunum (IC50, 15.2 micrograms/mL). Peppermint oil markedly attenuated contractile responses in the guinea pig taenia coli to acetylcholine, histamine, 5-hydroxytryptamine, and substance P. Peppermint oil reduced contractions evoked by potassium depolarization and calcium contractions evoked in depolarizing Krebs solutions in taenia coli. Potential-dependent calcium currents recorded using the whole cell clamp configuration in rabbit jejunum smooth muscle cells were inhibited by peppermint oil in a concentration-dependent manner. Peppermint oil both reduced peak current amplitude and increased the rate of current decay. The effect of peppermint oil resembled that of the dihydropyridine calcium antagonists. It is concluded that peppermint oil relaxes gastrointestinal smooth muscle by reducing calcium influx.
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PMID:The mechanism of action of peppermint oil on gastrointestinal smooth muscle. An analysis using patch clamp electrophysiology and isolated tissue pharmacology in rabbit and guinea pig. 164 42

1. Interactions between pulmonary cholinergic and noradrenergic nerves were studied in the innervated tracheal tube preparation isolated from guinea-pigs anaesthetized with urethane. Relaxations of the trachealis smooth muscle in response to postganglionic stimulation of the sympathetic nerve were recorded as decreases in the intraluminal pressure of the tracheal tube after the pressure had been raised with the stable thromboxane-mimetic, U46619. In contrast, contractions following preganglionic stimulation of the vagal nerve trunk were recorded as increases in intraluminal pressure. 2. In approximately half of the preparations studied, concurrent stimulation of of the vagal nerve trunk the vagal nerve trunk inhibited relaxation responses elicited by stimulation of the sympathetic nerves. The vagi were stimulated at parameters which caused no change in intraluminal pressure, excluding the involvement of postjunctional mechanisms. 3. The effect of simultaneous stimulation of the sympathetic nerve trunk was studied on contractile responses evoked by preganglionic stimulation of the vagus nerve. In 80% of the preparations tested the vagal responses were inhibited. This inhibitory effect of sympathetic nerve stimulation was antagonized by propranolol. 4. The potassium channel agonist, cromakalim, endothelins 1 and 3 and the neuropeptides, vasoactive intestinal peptide, neurokinin A and substance P, did not significantly modulate sympathetic nerve-induced relaxations. 5. The anticholinesterase drug, physostigmine, induced a concentration-dependent increase in the intraluminal pressure of the tracheal tube and potentiated the postjunctional action of exogenously applied acetylcholine to contract the guinea-pig trachealis muscle. In the presence of higher concentrations of physostigmine both vagally-induced contractions and sympathetic nerve-induced relaxations were reduced. Atropine blocked both the inhibitory effect of physostigmine on sympathetic relaxations and its postjunctional contractile action on the trachealis smooth muscle.6. It is concluded that, in the guinea-pig trachea, acetylcholine released endogenously from pulmonary parasympathetic nerves, either by anticholinesterase drugs or in response to nerve stimulation, can inhibit transmission in the adjacent sympathetic nerves via activation of prejunctional muscarinic heteroreceptors, probably of the M3 subtype.
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PMID:Evidence for inhibition of sympathetic neurotransmission by endogenously released acetylcholine in the guinea-pig trachea. 166 87

2-n-Butyl-4-chloro-5-hydroxy-methyl-1-[(2'-(1H)-tetrazol-5-yl)biph enyl-4- yl)methyl]imidazol potassium salt (DuP 753) is a nonpeptide angiotensin II receptor antagonist that inhibits the contractile effects of angiotensin II competitively and shows pA2 values of 8.27 on the rabbit aorta and jugular vein, 8.66 on the rat portal vein and stomach, 8.19 on the rat urinary bladder, and 8.36 on human colon, ileum, and urinary bladder. This agent (more than 10(-5) M) exhibits no agonistic activity and does not affect the contractile effects of norepinephrine, acetylcholine, bradykinin, desArg9-bradykinin, substance P, neurokinin A, neurokinin B, or bombesin in the various tissues. The present results demonstrate that DuP 753 is a potent nonpeptide antagonist with high affinity, specificity, and selectivity for the angiotensin receptor.
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PMID:DuP 753 is a specific antagonist for the angiotensin receptor. 167 62

The release of endogenous noradrenaline (NA) from slices of adult rat brainstem and ventral thoracic spinal cord was investigated using a fixed-volume incubation technique and HPLC with electrochemical detection. Incubation with potassium (15-50 mM) produced a dose-related increase in basal NA release that was calcium dependent. The potassium-evoked release of NA from spinal cord or brainstem slices was potentiated according to dose by preincubation with either (a) the selective alpha 2-adrenoceptor antagonist idazoxan (10(-6)-10(-4) M) or (b) the thyrotrophin-releasing hormone (TRH) analogue RX 77368 (pGlu-His-3,3'-dimethyl ProNH2; 10(-5) and 10(-4) M). Incubation of spinal cord slices with the NA uptake inhibitor maprotiline (1 microM) enhanced the effect of idazoxan but inhibited that of RX 77368. The effects of RX 77368 and potassium alone (15 mM) on NA release from both spinal cord and brainstem slices were reduced to basal levels with tetrodotoxin (10(-7) M). Similarly, preincubation of spinal cord, but not brainstem, slices with the insect neuropeptide proctolin (10(-4) M) significantly attenuated the potassium- or RX 77368-induced release of NA, whereas substance P (3 X 10(-5) and 1 X 10(-4) M) had no effect on either tissue. These results suggest that changes in NA release in the spinal cord and brainstem may mediate some of the actions of neuropeptides in ventral spinal cord, although the peptides may not be acting directly on the noradrenergic nerve terminals in these tissues.
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PMID:Ventral horn neuropeptides modulate the release of noradrenaline from tissue slices of rat brainstem and ventral thoracic spinal cord. 167 77

The effect of thermal stimulation on primary afferent neurons and its modulation by Ruthenium Red (RR) has been investigated in the isolated perfused rabbit ear with intact neuronal connection to the animal. Capsaicin, K(+)-depolarization as well as increasing the temperature of the perfusate to 50 degrees C, increased the amount of substance P-like immunoreactivity (SP-IR) in the outflow in a calcium-dependent manner. High performance liquid chromatography (HPLC) revealed that SP-IR which was released by thermal stimulation consisted of two components, one of which co-eluted with synthetic substance P. The same two components of SP-IR were also present in extracts of the auricular nerve and were released by capsaicin. RR attenuated the effect of capsaicin and thermal stimulation but did not reduce potassium-evoked release of SP-IR. To evaluate an inhibitory action of RR on the excitation of primary afferents, the isolated perfused ear with intact neuronal connection to the anaesthetized rabbit was used. Intraarterial injection of capsaicin or bradykinin as well as superfusion of a skin area of approximately 2 cm2 with water at 53 degrees C for 1 min, produced a depressor reflex. RR attenuated the response to thermal stimulation and to capsaicin, but did not block the bradykinin-induced depressor reflex. These results demonstrate that, in the rabbit ear, thermal stimuli excite primary afferent neurons and evoke the calcium-dependent release of neuropeptides from their peripheral terminals by a mechanism which is sensitive to RR.
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PMID:Activation of primary afferent neurons by thermal stimulation. Influence of ruthenium red. 169 Mar 58

The release of different forms of substance P-like immunoreactivity (SP-LI) from superfused slices of rat spinal cord was studied. The released SP-LI was characterized by reverse-phase high-performance liquid chromatography and radioimmunoassay with two antisera directed to the C- and N-terminal parts of SP, respectively. The SP-LI detected in the superfusates with the C-terminally directed antiserum was found to consist of (undeca) SP, SP-sulfoxide and a late eluting component which was not detectable with the N-terminally directed antiserum. This component was also found in neutral extracts of the spinal cord. Upon trypsin digestion, it produced SP-LI detectable with both C- and N-terminally directed antiserum which also coeluted with SP. From these results we conclude that this form of SP-LI most likely corresponds to an N-terminally extended form of SP. An increase of the potassium concentration in the superfusion fluid from 5 to 50 mM evoked an increased overflow of both SP and the N-terminally extended SP. The present results indicate that N-terminally extended SP is released by a calcium-dependent mechanism together with SP from terminals in the spinal cord in response to potassium stimulation.
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PMID:N-terminally extended substance P is released together with substance P from rat spinal cord. 169 19

We have previously found that antigenic stimulation of mast cells in the guinea pig superior cervical ganglion leads to membrane depolarization of principal neurons and a long-term increase in the efficacy of ganglionic transmission. In this study experiments were conducted to discern the histological, immunological and pharmacological characteristics of the mast cells within the superior cervical ganglion. Mast cells within the superior cervical ganglion could be stained with toluidine blue or berberine sulfate, the latter indicating that heparin-like molecules were present in the granules. Stainable mast cells were distributed throughout the ganglion with no gross evidence of regional localization. The number of mast cells stained with toluidine blue was reduced significantly (P less than 0.01) in contralateral ganglia that had been exposed to the sensitizing antigen (ovalbumin), indicating antigen-induced degranulation. The superior cervical ganglion contained 208 +/- 6 picomole of histamine (mean +/- SEM, n = 66). Ovalbumin evoked the release of histamine from the superior cervical ganglion in a concentration-dependent fashion. At maximally effective concentrations, ovalbumin released 33 +/- 2% of the total histamine stores (mean +/- SEM, n = 61). Similar values were obtained with antigen-challenged stellate ganglia. A temperature of 37 degrees C and an extracellular calcium concentration of 1 mM was required to elicit optimal antigen-induced responses. In addition to releasing histamine, antigenic stimulation of the ganglion resulted in a 3- to 5-fold increase in the synthesis and release of arachidonic acid metabolites including peptidoleukotriene, thromboxane B2, prostaglandins (PG) E2, F2 alpha, D2, the PGD2 metabolite 9 alpha 11 beta-PGF2, and the prostacyclin metabolite 6-keto PGF1 alpha. Various putative mast cell secretagogues were examined for their ability to activate the superior cervical ganglion mast cell, as indicated by evoked histamine release. In contrast to rat peritoneal mast cells, high concentrations of substance P, compound 48/80, and nerve growth factor failed to stimulate the ganglion mast cells. Preganglionic nerve stimulation, electrical field stimulation of axons and cell bodies, or depolarizing concentrations of potassium chloride also failed to activate the superior cervical ganglion mast cells. These results suggest that substances released by membrane depolarization do not influence the function of the resident mast cells. The results demonstrate that the mast cells within sympathetic ganglia can be actively sensitized to respond to specific antigen. These mast cells are similar to lung parenchymal mast cells with respect to histological, immunological and pharmacological characteristics...
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PMID:Mast cells in the guinea pig superior cervical ganglion: a functional and histological assessment. 169 91

Substance P, the widely distributed 11 amino acid neuropeptide, is present in up to 20% of vagal sensory cell bodies and the fibers emanating from them. To study the factors regulating the release of SP, vagal sensory (nodose or nodose/jugular) ganglia were obtained from neonatal rats and dissociated using neutral protease. Survival of plated neurons on collagen substrate was 10-20% at 2 weeks and 20-30% when neurons were plated over previously dissociated rat atriacytes. Substance P content was low in cultures for the first several days, then rose linearly to 0.1-0.2 pg/surviving neuron. Substance P was released into a 4.5 mM potassium medium at a steady rate of 0.036%/min. In 50 mM K+ supplemented medium, total release during 20 min increased 5-8-fold and steady-state release increased 4-5-fold to 0.15%/min. The sensory neuron specific excitatory neurotoxin, capsaicin, evoked SP release in similar amounts to 50 mM K+. Both net K(+)- and capsaicin-evoked, but not basal release were completely inhibited by 3.5 mM cobalt chloride. Bradykinin, 1-100 nM, stimulated SP release 2-4 times above basal levels. Forskolin and phorbol ester also increased SP release 1.5-3 times basal amounts. In summary, substance P is present in cultured vagal sensory neurons in amounts similar to in vivo and is released in response to sensory specific stimuli. These cultures should allow exploration of some of the tissue specific factors regulating neurotransmitter release in the sensory vagus nerve.
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PMID:Basal and stimulated release of substance P from dissociated cultures of vagal sensory neurons. 169 77


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