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 innervation in airway tissues from young adult (15-26 wk) and fetal (95/115 d gestation) pigs was compared in isolated tracheal and bronchial preparations subjected to electrical field stimulation. End-organ responsiveness to carbachol, substance P, isoprenaline, and VIP was present by 95 d gestation. Electrical field stimulation (0.5-20 Hz, 70 V, 0.5 ms) resulted in a frequency-dependent contraction that was blocked by atropine (10(-6) M) and TTX (10(-6) M) at both ages. However, there was a 10-fold increase in threshold in the fetal airways because contractions were evoked at frequencies of approximately 5 Hz in the fetus compared with 0.5 Hz in the young adult airways. In the young adult airways, there were atropine-resistant contractions at longer pulse durations (1-5 ms, 20 Hz), but not usually in the fetus. The atropine-resistant contractions were not blocked by TTX. Capsaicin (10(-6) M) produced no contraction in the pig airway. In tissues contracted using the ED50 of carbachol, electrical stimulation (1-20 Hz, 70 V, 1 ms) caused marked relaxation, however, compared with those in the young adult, fetal responses were weak or absent. Propranolol (10(-6) M) partially reduced the relaxation of the young adult bronchus (approximately 25%), but it had little effect on responses in the other young adult and fetal preparations. Therefore, the inhibitory innervation of pig airways was predominantly nonadrenergic and the excitatory component was cholinergic. Neither of these components was fully developed in the fetus close to term.
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PMID:Inhibitory and excitatory responses to field stimulation in fetal and adult pig airway. 237 98

1. Opioid receptors have been demonstrated on sensory fibres in the vagus nerve. Non-cholinergic (NC) neural bronchoconstriction in guinea-pig is due to release of neuropeptides from sensory nerve endings. We have therefore studied the effect of opioids on this NC bronchoconstriction in the anaesthetized guinea-pig. 2. Bilateral vagal stimulation (5 V, 5 ms, 10 Hz) caused reproducible bronchoconstriction in guinea-pigs which was reduced by atropine (1 mg kg-1), but the NC component was unaffected by hexamethonium (10 mg kg-1). 3. NC bronchoconstriction was reduced by morphine in a dose-dependent manner (ED50 = 132 micrograms kg-1 with a maximal inhibition of 79 +/- 2.1% at 1 mg kg-1). Yohimbine (0.5 mg kg-1) did not alter the inhibitory effect of morphine (1 mg kg-1). 4. The inhibitory effect of morphine was completely reversed by naloxone (1 mg kg-1) which had no effect on NC bronchoconstriction. Propranolol (1 mg kg-1) significantly increased the NC bronchoconstrictor response but did not significantly alter the inhibition by morphine. 5. The selective mu-opioid receptor agonist Tyr-(D-Ala)-Gly-(N-Me-Phe)-Glyol (DAGOL) was significantly more potent than morphine with an ED50 of 5.4 micrograms kg-1 and complete inhibition at 100 micrograms kg-1. The delta-agonist Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE) was less potent than DAGOL with an ED50 of 28 micrograms kg-1 and a maximal inhibition of only 50 +/- 5% at 100 micrograms kg-1. The delta-agonist Tyr4D-Pen)-Gly-Phe-D-Pen) (DPDPE) was less potent than DAGOL with an ED5o of 28pgkg-1 and a maximal inhibition of only 50 + 5% at lOOPgkg- . The Kappa-receptor agonist, U-50,488H had no inhibitory effect on the NC bronchoconstrictor response. 6. The bronchoconstrictor responses to exogenous substance P (25 pgkg- 1) or acetylcholine (25 pg kg- 1) were unaffected by morphine (500 pg kg- 1). 7. We conclude that opioids inhibit the NC bronchoconstrictor response to vagal stimulation via an action on mu-opioid receptors localized to sensory nerve endings in the airway.
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PMID:Opioid modulation of non-cholinergic neural bronchoconstriction in guinea-pig in vivo. 246 5

1. The effects of continuous stimulation of the peripheral end of the ascending cervical sympathetic nerve were compared with those of intermittent stimulation, so arranged as to deliver the same total number of impulses, in cats under chloralose anaesthesia. 2. Continuous stimulation caused a flow of saliva at 5-10 Hz, but not at 2 Hz. In contrast, the same total number of impulses delivered intermittently in bursts elicited a prompt secretion at a frequency as low as 20 Hz for 1 s at 10 s intervals (corresponding to 2 Hz continuously) and a significantly higher rate of secretion at 50 Hz in bursts than that obtained in response to 5 Hz continuously. 3. Continuous stimulation also caused a rise in submandibular vascular resistance (s.v.r.), which persisted throughout the period of stimulation, and was followed immediately thereafter by an intense but transient fall in s.v.r. During stimulation in 1 s bursts, each burst was followed first by a brief rise in s.v.r. and shortly after by a fall. The balance between these two components varied widely between individual animals but often led to an overall fall in s.v.r. during stimulation i.e. complete reversal of the mean vascular effect. A further fall in s.v.r. was then recorded when the stimulus was discontinued. 4. Propranolol (1.0 mg/kg) reduced but failed to abolish the secretory response. It also altered the balance between the two phases of the vascular response slightly in favour of a rise in s.v.r. during stimulation, without apparently affecting the size of the after-dilatation. 5. Pre-treatment with dihydroergotamine (1.0 mg/kg) invariably blocked secretion and revealed a small vasodilator response during sympathetic stimulation with either pattern of stimulation; it also blocked the after-dilatation. 6. Following combined pre-treatment with propranolol and dihydroergotamine, to produce total adrenergic blockade, there was a small residual vasoconstrictor component which amounted to an increase in mean s.v.r. of about 20% during stimulation at 10 Hz continuously. This may have been due to release of neuropeptide Y (NPY). 7. Small but significantly greater amounts of NPY were released into the effluent blood during stimulation of the ascending cervical sympathetic nerve at 70 Hz in bursts than during continuous stimulation. No significant release of vasoactive intestinal peptide (VIP), somatostatin, bombesin, substance P or calcitonin gene-related peptide (CGRP) was observed during stimulation at any frequency.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of stimulating the sympathetic innervation in bursts on submandibular vascular and secretory function in cats. 289 12

The effects of substance K (SK), a newly discovered tachykinin, on the cardiovascular and sympathetic system were evaluated in the pithed rat preparation and in the in situ domestic pig heart. In pithed rats, SK (10 nmol/kg, IV) produced a triphasic mean blood pressure (MAP) response: short depressor, short pressor (+11 +/- 1 mmHg), and prolonged depressor phase (-9 +/- 1 mmHg, n = 9-24, p less than 0.001). Neither effect was significantly affected by pretreatment with propranolol (2 mg/kg) or phentolamine (1 mg/kg). The pressor response was accompanied by increased heart rate (HR): 41 +/- 4 beats/min, while lower doses produced a decrease: -8 +/- 2 beats/min (p less than 0.01). Propranolol abolished the increase in HR. SK inhibited the pressor response evoked by electrical stimulation of the spinal cord (SCS) and by Arg8-vasopressin (AVP). SK increased circulating levels of epinephrine and norepinephrine but did not change release of catecholamines evoked by SCS. Direct intracoronary injections of SK (0.3-100 nmol, intact pig heart) increased coronary blood flow; higher doses decreased MAP and increased HR. These results indicate that: SK can produce pressor and depressor effects in the rat and is a potent coronary dilator in the pig. In the pithed rat SK causes catecholamine release which mediates its cardiac accelerator effect and it antagonizes adrenergic and non-adrenergic pressor stimuli.
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PMID:Substance K: vascular and cardiac effects in rat and pig. 300 74

Propranolol-resistant neurogenic relaxation persisted in (carbachol-contracted) guinea-pig tracheae already relaxed by supramaximal concentrations of vasoactive intestinal polypeptide (VIP). Also, VIP relaxed preparations that were under neurogenic inhibition. In hilus bronchi, about 60% of a neurogenic contraction was atropine-resistant. (Arg5, D-Trp7.9) SP 5-11 specifically antagonized this contraction and those produced by exogenous substance P. Substance P, but not VIP, seems to be involved in nerve-mediated effects on guinea-pig airway tone.
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PMID:Evidence against vasoactive intestinal polypeptide (VIP) as a dilator and in favour of substance P as a constrictor in airway neurogenic responses. 619 24

We studied effects of nicotinic, muscarinic, serotoninergic, dopaminergic, adrenergic, vasoactive intestinal peptide (VIP) antagonists, VIP, nitric oxide-synthase inhibitors and stimulators alone and in combination with tetrodotoxin on substance P (SP)-stimulated intraluminal tone of the isolated proximal, middle and distal rat colon. Tetrodotoxin significantly enhanced SP-stimulated intraluminal tonic pressure in the distal, but not in the middle and proximal colon. N omega-nitro-L-arginine methylester enhanced SP stimulation in all colonic segments, whereas L-arginine inhibited it partially and D-arginine did not affect it. Atropine and hexamethonium partially inhibited SP stimulation of the middle and distal colon. Tetrodotoxin completely abolished the effects of L-arginine, atropine and/or hexamethonium on SP stimulation. Propranolol, phentolamine, reserpine, telenzepine, naloxone, Mr 2266, a VIP antagonist (H9935) and ketanserin did not affect SP-induced colonic muscle stimulation. VIP strongly reduced SP-stimulated intraluminal pressure in all colonic segments. VIP(10-28), a putative VIP antagonist, produced similar inhibition of SP-stimulated intraluminal tonic pressure, but did not affect N omega-nitro-L-arginine methylester-induced enhancement of SP-stimulated intraluminal pressure in any segments. It is concluded that in the isolated rat colon SP-stimulated intraluminal pressure (mainly generated by circular muscles) by a direct action on colonic muscles over the whole colonic length and by simultaneous activation of neural cholinergic excitatory pathways in the middle and distal, of noncholinergic excitatory pathways in the proximal colonic segment, and by activation of nitric oxide-dependent inhibitory neural pathways. VIP seems not to be directly involved in this inhibitory pathway.
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PMID:Substance P activates rat colonic motility via excitatory and inhibitory neural pathways and direct action on muscles. 752 33

The substance P when administered intracerebroventricularly (15 nmol) led to a transformation of feeding elicited by threshold electrical stimulation of the lateral hypothalamus into an escape reaction in rabbits. Obsidan, Inderal (0.25 and 0.5 mg) and droperidol (0.3 mg) injected intravenously were found to restore the functional properties of the hypothalamic feeding centre. No changes in the escape reaction were observed after kalipsol (ketaminum) administration. The data obtained suggest the important role of the catecholaminergic brain structures in the mechanisms of the transformation of the functional properties of the hypothalamic feeding centre under the influence of the substance P.
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PMID:[A neurochemical analysis of the substance P-induced reordering of the feeding behavior evoked by electrical stimulation of the lateral hypothalamus]. 768 18

In the present investigation changes of pulmonary and carotid arterial pressure in response to injection of substance P(SP) into the 4th ventricle of rabbits were studied. The results were as follows: (1) Intraventricular (ivt.) injection of SP could induce either an increase or a decrease in pulmonary arterial pressure as well as carotid arterial pressor response and bradycardia. (2) Bilateral cervical vagotomy could initiate a definite pulmonary pressor response and a marked decrease in the bradycardiac response to injection of SP in those rabbits originally showing a depressor response of pulmonary artery to SP. (3) Pretreatment by i.c.v. and i.v. phentolamine or alpha 1 blocker, prazosin, could block both the SP-induced pulmonary and carotid pressor responses. (4) alpha 2 blocker, yohimbine, or naloxone could enhance the pressor responses in the both arteries. (5) Propranolol had no effect on the pressor responses in both arteries. (6) The cardiovascular responses to SP could be blocked by the SP blocker (D-Pro2.D-Trp7.9)-SP. It is assumed that increase of SP in the brain may induce an increase in both the pulmonary and carotid arterial pressures and bradycardia by activating the SP receptors. The central mechanism responsible for the SP- induced pressor response involves the participation of adrenergic alpha 1 receptor activities, while the central adrenergic alpha 2 receptor system as well as the endorphin system exerts an inhibitory modulation on the central SP-induced pressor pathway. It appears that SP, catecholamine and opiate substance are all involved in the regulation of blood pressure by brain stem.
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PMID:[Effect of intraventricular injection of substance P on pulmonary and carotid arterial pressure in rabbits]. 768 52

Substance P (SP, 1 microM) when incubated with minced von Ebner's glands for 15, 30, and 60 min, stimulated secretion of lingual lipase (12.14% +/- 0.90) and amylase (8.30% +/- 0.42). Only 10 microM of the SP receptor antagonist CP-96,345 significantly inhibited SP-evoked secretion. D-Pro2-D-Phe7-D-Trp9-SP (Ia), D-Pro2-D-Trp7,9-SP (Ib), D-Arg1-D-Trp7,9-D-Leu11-SP (Ic), or 1 microM CP-96,345 were not effective, suggesting that the SP receptor of von Ebner's gland might be an isoform. Propranolol and timolol, beta 1/beta 2-adrenergic receptor antagonists were not effective and the cholinergic receptor antagonist, atropine, was effective in only slightly reducing amylase secretion but not lingual lipase. Differential secretion of the two enzymes was observed for basal and stimulated secretion. Thus, exocytosis may not be the only pathway involved in SP-evoked protein secretion.
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PMID:Effect of substance P and receptor antagonists on secretion of lingual lipase and amylase from rat von Ebner's gland. 914 1

This study has investigated the relative involvement of cholinergic, adrenergic, nitric oxide and tachykininergic transmission in extrinsic neural influences on the lower oesophageal sphincter (LOS) in urethane anaesthetized ferrets. A micromanometric assembly (OD 1.75 mm) incorporating a sleeve sensor was used for high-fidelity oesophageal, LOS and gastric pressure measurement at low perfusion rates (< 0.1 ml/min). The LOS response to vagal and splanchnic nerve stimulation (0.5 ms pulse width, 10 s duration) was frequency- and voltage-dependent. LOS responses to stimulation at 20 V, 10 Hz were investigated in separate groups of animals with either L-NAME (100 mg/kg), hexamethonium (15 mg/kg), guanethidine (5 mg/kg), CP96,345 (NK-1 antagonist, 4 mg/kg), atropine (0.4 mg/kg) or propranolol (1 mg/kg). Propranolol treatment was followed by yohimbine (1 mg/kg) and prazosin (0.25 mg/kg). Vagal stimulation caused an immediate decrease in LOS pressure, followed by increase on cessation of stimulation, followed by a prolonged decrease (77 +/- 2%) for up to 5 min. L-NAME did not affect inhibition, but increased excitation 4-fold (p < 0.001). Guanethidine and CP96,345 had no major effect. Hexamethonium decreased the inhibitory (p < 0.05) and excitatory (p < 0.01) responses. Atropine reduced the excitatory response (p < 0.05). Some inhibition still remained if all treatments were combined. Splanchnic stimulation reduced LOS pressure by 70 +/- 6% for 101 +/- 17 s. L-NAME, guanethidine, hexamethonium and CP96,345 all independently significantly reduced inhibition. The combination of guanethidine and CP96,345 usually abolished splanchnic-induced inhibition. Atropine was without effect. Propranolol (1 mg/kg) changed the splanchnic-induced response from mainly inhibition to excitation (100 +/- 44% increase). LOS responses to noradrenaline (1-10 micrograms close IA) showed similar features to responses to splanchnic stimulation. We conclude that vagal stimulation evokes LOS relaxation via activation of established cholinergic and NANC mechanisms and other, unidentified mechanisms. Splanchnic stimulation activates adrenergic neurones probably via nicotinic and non-nicotinic ganglionic mechanisms, which in turn elicit beta adrenergic inhibitory effects on the LOS. Splanchnic stimulation also antidromically activates spinal afferent fibres. These may release substance P from peripheral myenteric plexus and prevertebral ganglionic endings causing activation of myenteric NANC inhibitory neurones and sympathetic neurones, respectively.
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PMID:Vagal and sympathetic influences on the ferret lower oesophageal sphincter. 940 23


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