Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metoclopramide has a dual effect on intestinal smooth muscle. Low concentrations of metoclopramide cause potentiation of the responses to substance P, acetylcholine, histamine and barium chloride on the guinea-pig ileum. Higher concentrations produce a depression of smooth muscle responses which is characteristic of the tertiary amine local anesthetics. Neural pathways are involved in the mechanism of potentiation, since the enhancement of the responses to the agonists is abolished by tetrodotoxin. Atropine partially antagonizes the potentiating effect of metoclopramide implying that activation of muscarinic receptors is a contributing factor, but this does not fully explain the potentiation.
 ...
PMID:The effects of metoclopramide in modifying the response of isolated guinea-pig ileum to various agonists. 0 87

Changes of potentials in the longitudinal and circular muscles of the small intestine and impulse frequency in mesenteric afferent fibers during intraluminal administration of sucrose solution were studied in cats before and after effects of adreno- and cholinolytic agents. Reserpine, dihydroergotamine, and N-cholinoblocking agents (hexonium or benzohexonium) increased the excitatory effect of sucrose whereas atropine abolished the effect. Atropine in combination with dihydroergotamine did not abolish the activating effect of sucrose. The latter seems to be unrelated to stimulation of either cholinergic or adrenergic intramural neurons. Involvement of substance P is suggested.
 ...
PMID:[Analysis of afferent impulsation and muscle potentials of the small intestine in response to sucrose]. 46 34

Since the original observations by Von Euler and Gaddum, considerable interest has developed regarding the role of substance P in smooth muscle function. The purpose of the present investigation was to evaluate the effect of intravenously administered substance P on the vivo motor function of the lower esophageal sphincter (LES). Intraesophageal pressures were monitored by an assembly of polyvinyl catheters attached to pressure transducers and a recorder. The catheters were continuously perfused with bubble-free water. Administration of 5, 10, 25, 50, and 100 ng per kg of substance P stimulated the LES, respectively, 16, 32, 57, 147, and 169% above control values. Tetrodotoxin, phentolamine, hexamethonium, methysergide, and bilateral cervical vagotomy did not alter the response of the LES to substance P. Atropine in 40-, 250-, and 500-microgram per kg doses significantly but partially inhibited the response of the LES to substance P. It is concluded that subtance P is a potent stimulant of the LES. The stimulatory effect of substance P may involve both cholinergic muscarinic and noncholinergic mechanisms. It is conceivable that substance P may be a modulator of LES pressure, although the exact physiological significance is not clear at the present time.
 ...
PMID:Effect of substance P on the lower esophageal sphincter of the opossum. 66 13

Tachykinin receptors mediating substance P-induced secretion were examined in muscle-stripped segments of guinea-pig ileum set up in flux chambers. Changes in the short-circuit current (Isc) served as an index of active, electrogenic ion transport. Substance P evoked a transient increase in Isc which was concentration-dependent. The maximal change in Isc occurred at 1 microM concentration. [Sar9,Met(O2)11]-substance P, a neurokinin 1 (NK-1) receptor agonist, evoked a similar concentration-dependent increase in Isc. [Nle10]NKA(4-10) (1 microM) or [Pro7]NKB (1 microM), selective NK2 and NK3 agonists, respectively, had minimal effects on Isc. CP-96,345 (5 microM), a nonpeptide NK-1 antagonist, and the peptide NK-1 antagonist, GR82334 (1 microM), reduced the secretory response to substance P (50 nM) in the presence and absence of tetrodotoxin (0.2 microM). The NK2 antagonist, [Tyr5,D-Trp6,8,9,Arg10]NKA(4-10) MEN 10207 had no effect on the substance P response. Tetrodotoxin (0.2 microM) significantly reduced, but did not abolish the Isc response to substance P (1 microM) and [Sar9,Met(O2)11]substance P (1 microM). The substance P response was unaltered by 5 microM atropine and 50 microM mecamylamine. Piroxicam (10 microM) or pyrilamine (10 microM) or a combination of both had no effect on the tetrodotoxin-resistant substance P response. Electrical field stimulation evoked a biphasic increase in Isc which was significantly reduced by 0.2 microM tetrodotoxin. Atropine (5 microM) reduced the first peak of the biphasic response and mecamylamine (50 microM) had no effect. Similarly, 5 microM CP-96,345 and 1 microM GR82334 did not alter the EFS-induced change Isc. The results suggest that substance P-evoked secretory responses are independent of histamine or prostaglandins. Substance P responses are mediated by an NK-1 receptor type on enteric neurons and possibly epithelial cells.
 ...
PMID:Neurokinin 1 receptors mediate substance P-induced changes in ion transport in guinea-pig ileum. 127 53

The mode of action of the excitatory neuropeptide substance P was studied on the circular muscle of the guinea pig ileum in vitro. Atropine or tetrodotoxin strongly inhibited substance P-induced phasic contractions. The atropine-resistant part of the circular response was blocked by tetrodotoxin. A newly-developed method for quantitative evaluation revealed a rightward displacement of the substance P concentration-response curve, as well as a strong depression of the maximum effect, in the presence of atropine. These results indicate that cholinergic (and probably also non-cholinergic) excitatory neurons mediate phasic contractions due to substance P. The tonic component of the substance P-induced contraction was slightly reduced by atropine.
 ...
PMID:Cholinergic neurons are involved in the effect of substance P on the circular muscle of the guinea pig small intestine. 128 67

The effects of electrical field stimulation (EFS) of rabbit middle cerebral arteries were examined using wire-mounted arterial segments. EFS of segments maintained at rest tension caused a tetrodotoxin-sensitive sympathetic contraction. In agonist-contracted segments maintained at approximately 60% of tissue maximum force, EFS caused a relaxation in two thirds of the preparations. Maximum response (mean +/- SEM) was 33 +/- 3.5% of maximal relaxation. The EFS relaxation was tetrodotoxin-sensitive but was not blocked by either chronic surgical sympathectomy or exposure to guanethidine (5 microM). Electron microscopy of chromaffin-fixed arterial sections showed the presence of chromaffin-positive large and small vesicles. Within the same sheath of Schwann were also a smaller number of nerve profiles containing many small clear vesicles. Removal of the vascular endothelium or treatment with atropine (10 nM) eliminated the EFS relaxation in approximately 50% of the segments and reduced the response in another 35-40%; in the remainder, relaxation was unaffected. Combined data for endothelium removal and atropine treatment showed that each caused a significant (p less than 0.01) reduction in the EFS relaxation. Atropine also significantly reduced EFS relaxation in guanethidine-treated segments. There was no reduction in EFS relaxation after procedures that antagonized ATP- or substance P-mediated relaxations. These results indicate that EFS of precontracted rabbit middle cerebral artery causes a neurogenic nonadrenergic relaxation. The neuroeffector mechanism mediating this response has a predominantly cholinergic endothelium-dependent component as well as a noncholinergic endothelium-independent component.
 ...
PMID:Electrical field stimulation-mediated relaxation of rabbit middle cerebral artery. Evidence of a cholinergic endothelium-dependent component. 134 15

The secretion of ileal neurotensin (NT) results from events occurring at the apical and basal side of the N-cells. The hypothesis of a functional relationship between cholinergic and peptidergic neurones with the N-cell was investigated in the present study utilizing the isolated vascularly perfused rat ileum. Intraarterial methacholine (MC, 10(-4) M) evoked a prompt and well sustained release of NT in the portal effluent (plateau value at 500% of basal). This effect was dose-dependent over the range of 10(-6) M to 10(-4) M. Bombesin (B) provoked a dose-dependent peak secretion of NT (800% of basal at 10(-7) M) followed by a rapid return to almost basal levels. The B-induced NT release remained unaltered upon 10(-6) M tetrodotoxin (TTX) or 10(-5) M atropine infusion. Substance P (SP) potently stimulated the release of NT. The maximal response, consisting of a sustained secretion, was observed at a concentration of 10(-7) M (350% of basal) while 10(-6) M SP induced a transient release. TTX or atropine did not reduce significantly the SP-induced secretion of NT. Neurokinin A and B did not increase NT concentrations in the portal effluent. B synergistically increased the secretion of NT induced by SP. Atropine or TTX did not modify the effect of combined SP and B infusion. MC potentiated the release of NT induced by B but not that evoked by SP. Combined infusion of SP, B and MC produced the largest output of NT. In conclusion, B, SP and MC are strong stimulants of NT release in rats. In addition, the cooperative effects of these transmitters argue in favor of a complex functional relationship between the intramural nervous network and the intestinal N-cells in rats.
 ...
PMID:Cooperative effects of bombesin, substance P and methacholine on the release of intestinal neurotensin in rats. 137 13

The tachykinins substance P (SP) and neurokinin A (NKA) have been shown to induce airway smooth muscle contraction in mature animals, and the enzyme neutral endopeptidase (NEP) modulates this effect. We evaluated maturation of SP- and NKA-induced tracheal smooth muscle contraction and modulation of their effects by NEP in anesthetized, paralyzed, and artificially ventilated piglets less than 4 days, 2-3 wk, and 10 wk of age. Tracheal smooth muscle tension was measured in vivo from an open tracheal segment by use of a force transducer. Intravenous SP caused a dose-dependent increase in tracheal tension in all three age groups; however, the response in less than 4-day-old piglets was significantly weaker than in 2- to 3- and 10-wk-old piglets. NKA caused a dose-dependent increase in tracheal tension only in 2- to 3- and 10-wk-old piglets. The response of tracheal tension to NKA was weaker than the response to SP in all age groups. Atropine (2 mg/kg) significantly diminished the responses of tracheal tension to SP and NKA, indicating a cholinergic contribution to these responses at all ages. Intravenous thiorphan, a known NEP inhibitor, potentiated the effects of SP only in 2- to 3- and 10-wk-old piglets and did not affect the response of tracheal tension to NKA at any age. Biochemical analyses demonstrated a significant increase in tracheal NEP activity in comparably aged piglets over the first 10 wk of life.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tracheal smooth muscle responses to substance P and neurokinin A in the piglet. 137 11

The effect of ozone (3 ppm, 15-120 min) on bronchial reactivity in the guinea-pig was studied. Ozone induced marked (6-250-fold) bronchial hyperreactivity (BHR) to a range of inhaled, but not intravenous bronchoconstrictors. The degree of BHR was related to the duration of prior ozone exposure. The glutathione redox status was shifted to a more oxidized state in lung after 120 min ozone treatment, although no changes were found in the energy status of lung tissue, as judged by the concentrations of adenosine phosphates. Ascorbic acid pretreatment prevented BHR induced by 30 min ozone exposure. Neutral endopeptidase inhibitors elicited BHR to both substance P and histamine, but did not further enhance bronchoconstriction to substance P after ozone exposure for 120 min. Neither mepyramine, fentanyl, indomethacin nor a 5-lipoxygenase inhibitor (BW B70C), given prior to ozone exposure prevented the induction of BHR to histamine. Atropine or bilateral vagotomy reduced BHR after a 120-min, but not 30-min exposure to ozone. We conclude that in the guinea-pig, ozone induces non-specific, route-dependent BHR by oxidative injury, reducing airway NEP activity and enhancing the cholinergic and peptidergic component to bronchoconstriction. Neither cyclooxygenase nor 5-lipoxygenase products appear to play a role in ozone-induced BHR in this animal model.
 ...
PMID:Mechanisms contributing to ozone-induced bronchial hyperreactivity in guinea-pigs. 137 22

The mammalian tachykinin neuropeptides substance P (SP) and neurokinin A (NKA) are present in the airways of several species and are involved in control of bronchomotor tone. We investigated the effect of SP and NKA on various respiratory and cardiovascular parameters in anaesthetized sheep. Dose-dependent decrease in dynamic compliance (Cdyn) and increase in respiratory resistance (RL) occurred with intravenous administration of SP. The predominant effect of NKA was on Cdyn with little or no effect on RL. Consequently SP is a more potent bronchoconstrictor than NKA in the sheep and affects both central and peripheral airway tone. The sensitivity to SP and NKA and the order of potency found suggests the NK-1 receptor predominates in sheep airways. Atropine and the ganglion blocker hexamethonium markedly reduced the bronchoconstriction caused by SP. SP and NKA were equipotent in causing a significant reduction in respiratory rate. SP caused a fall in mean blood pressure while NKA caused mild vasoconstriction. Neither peptide affected heart rate. We concluded that SP is a more potent bronchoconstrictor than NKA in the sheep and that the mechanism of action is mainly indirect involving modulation of postganglionic cholinergic nerve endings.
 ...
PMID:The effect of tachykinins on sheep bronchomotor tone. 137 45


1 2 3 4 5 6 7 8 9 10 Next >>