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)

Intracerebroventricular (i.c.v.) pretreatment of Wistar rats with the catecholaminergic neurotoxin, 6-hydroxydopamine, significantly reduced noradrenaline in the pons/medulla (by 73%) and almost abolished the noradrenaline levels in the spinal cord (by 89%). The pressor response of these animals to i.c.v. angiotensin II (ANGII, 10 ng) was significantly attenuated. In contrast, there was no significant effect on the pressor response to i.c.v. substance P (SP, 100 ng). The results provide evidence that different central pathways mediate the pressor response to ANGII and SP.
 ...
PMID:Central noradrenergic pathways are not involved in the pressor response to intracerebroventricular substance P. 246 Mar 63

The cellular localization of vascular plasma membrane aminopeptidase M (AmM; EC3.4.11.2) was examined in cultured porcine aorta endothelium and smooth muscle cells. AmM was 14-fold higher on smooth muscle (117 +/- 16 units/mg) than on endothelium (8.4 +/- 0.2). Proportional to its cellular distribution, AmM hydrolyzed the N-terminus of kallidin to produce bradykinin, and degraded des(Asp1)angiotensin I, angiotensin III, hepta(5-11)substance P and Met5-enkephalin. In contrast, bradykinin, angiotensin II and substance P were resistant to AmM-mediated hydrolysis. Peptide metabolism was optimal at pH 7.0 and was inhibited by o-phenanthroline, bestatin (Ki = 2.2 +/- 0.1 microM) and amastatin (Ki = 25 +/- 5 nM). Des(Asp1)angiotensin I and angiotensin III had the highest affinity (lowest Km) for AmM (Km = 2.2 +/- 0.5 and 2.0 +/- 0.4 microM respectively), followed by hepta(5-11)substance P (53.9 +/- 1.7 microM) and Met5-enkephalin (75.7 +/- 3.5 microM). In contrast, maximal velocities of hydrolysis were higher for Met5-enkephalin (313 +/- 2 nmol/min/mg) than for hepta(5-11)substance P (109 +/- 18 nmol/min/mg) or angiotensin III (26.5 +/- 1.0 nmol/min/mg). As expected for hydrolysis by a common enzyme, AmM-mediated enkephalin degradation was inhibited competitively by angiotensin III (Ki = 0.34 +/- 0.04 microM), hepta(5-11)substance P (43.7 +/- 6.3 microM) and kallidin (62 microM). These data suggest that vascular AmM may modulate vasoactive peptide levels in vivo, particularly within the microenvironment of endothelial and smooth muscle cell surface receptors.
 ...
PMID:Metabolism of vasoactive peptides by vascular endothelium and smooth muscle aminopeptidase M. 246 80

1. To learn how pulmonary vascular injury alters the ability of the lung to metabolize vasoactive autacoids, lung vascular lesions were produced in rats by a single subcutaneous injection of monocrotaline (90 mg kg-1), and the blood pressure responses to angiotensin I (AI), angiotensin II (AII), bradykinin, prostaglandin E2 (PGE2) and substance P were examined. Vasoactive agents were given intravenously or intra-arterially. 2. On histological examination of the lung at 3 weeks after monocrotaline treatment, degeneration or necrotization of endothelial cells was evident. 3. The conversion of AI to AII was only slightly depressed by monocrotaline treatment. On the other hand, the depressor response to intravenously injected bradykinin was enhanced in monocrotaline-treated rats. When the rats were pretreated with indomethacin the depressor response to intravenous bradykinin was the same for both control and monocrotaline-treated groups which suggests that endogenous prostaglandins are involved in the enhancement of the response to bradykinin. 4. In monocrotaline-treated rats the depressor response to intravenous PGE2 was significantly enhanced depending on the period following the treatment, while that to the intra-arterial injection did not differ from control. 5. The data suggest that monocrotaline-induced lung injury impairs the metabolism of PGE2 during pulmonary circulation but has little effect on the conversion of AI to AII and the degradation of bradykinin in rats.
 ...
PMID:Alteration of fate of vasoactive autacoids in pulmonary circulation following monocrotaline-induced lung vascular injury in rats. 246 24

1. The effect of an acid extract of the carp intestinal bulb (ECI) on guinea-pig ileum longitudinal smooth muscle (GPLM) and carp intestinal bulb longitudinal smooth muscle (CIBLM) was examined. 2. ECI caused a concentration-dependent contraction of GPLM and CIBLM. This ECI-induced response was reduced by atropine to 30-40% of the control, indicating that part of the contracting activity of ECI is attributable to acetylcholine. The atropine-resistant contracting activity of ECI was not mediated by histamine, 5-hydroxytryptamine, ATP, ADP, angiotensin II, neurotensin, vasoactive intestinal peptide or an opioid peptide. 3. The active material mediating the atropine-resistant contracting activity is probably a peptide, because the contraction in response to ECI was abolished on incubation with pepsin or alpha-chymotrypsin. 4. [D-Pro2, D-Trp7,9]-substance P, [D-Pro4, D-Trp7,9]-substance P (4-11) decreased the atropine-resistant contracting activity of ECI as did desensitization induced by substance P. 5. On a Sephadex G 25 column, the active material was eluted as one peak. The active fractions were pooled and then applied to another Sephadex G25 column to compare the Ve/Vo value for the active material with those for peptides of known molecular weights. The molecular weight of the active material was estimated to be 1200-1700 (1410 +/- 70, n = 6). 6. The results indicate the presence of a substance P-like peptide in the carp intestinal bulb.
 ...
PMID:Presence of a substance P-like peptide in an acid extract of the intestinal bulb of the carp (Cyprinus carpio). 246 88

The tachykinins eledoisin, substance P and kassinin were administered by pulse intracerebroventricular (ICV) injections to cats made thirsty by ICV angiotensin II, 100 ng per cat. Eledoisin, 100 ng per cat, produced an inhibition of drinking which was larger (56.0 vs. 45.2%) and lasted longer than that evoked by 400 ng per cat of substance P. Kassinin, 100 ng per cat, did not evoke any effect at all. The treatment with these peptides neither produced signs of discomfort nor induced any other behavioural alteration. The results of present experiments suggest that the antidipsogenic effect of tachykinins is a phenomenon of general interest among mammals.
 ...
PMID:Inhibitory effect of intracranial injections of tachykinins on angiotensin-induced drinking in the cat. 246 87

High-affinity binding sites for endothelin have been found in a human placenta membrane preparation. 125I-endothelin bound to placenta membranes at 20 degrees C with an association half-time of 30 min, whereas the binding was only slowly reversed with a dissociation half-time of 250 min. In saturation experiments, a single class of high-affinity binding sites was identified with an apparent dissociation constant (KD) of 24 pM and a maximal density of 240 fmol per mg of protein. The binding of 125I-endothelin was half-maximally inhibited by cold endothelin at a concentration (IC50) of 140 pM. In contrast, no inhibition was found at 10(-4) M for a variety of vasoactive peptides such as angiotensin II, vasopressin, neuropeptide Y, substance P, CGRP, bradykinin, leucine enkephalin or dynorphin A. Similarly, the binding was modulated neither by the calcium channel blockers nifedipine, verapamil or diltiazem, nor by the calcium channel agonist Bay k 8644. There was also no effect with the structurally-related bee venom apamin. Using this membrane preparation, endothelin-like activity could be measured in the medium of cultured human endothelial cells by competition binding technique.
 ...
PMID:Specific receptors for endothelin on membranes from human placenta. Characterization and use in a binding assay. 254 8

The centrally induced effects of angiotensin II and substance P on the cardiovascular system and on neuronal efferent activity of the splanchnic, renal, and adrenal nerves were investigated in chronically instrumented conscious rats. The pressor responses to substance P injected into the lateral brain ventricle were accompanied by marked and short latency increases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a rise in plasma noradrenaline and adrenaline. Behaviorally, an arousal-type reaction was observed. In contrast, the pressor responses to intracerebroventricular angiotensin II were associated with initial decreases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a fall in plasma noradrenaline at the time of the maximal blood pressure increase. In some but not all animals, a second blood pressure peak associated with increases in heart rate and splanchnic nerve activity was observed after several minutes. Incomplete chronic sinoaortic baroreceptor deafferentiation prevented the angiotensin II-induced fall in heart rate but not the initial fall in splanchnic nerve activity. The decreases in splanchnic nerve activity also occurred in diabetes insipidus rats and persisted in Long Evans rats after vascular vasopressin receptor blockade with d(CH2)5AVP, despite marked reductions of the pressor responses in both groups. Peripheral alpha-adrenoceptor blockade with prazosin or ganglion blockade with hexamethonium inhibited the central angiotensin II pressor responses only in combination with vasopressin receptor blockade. On the other hand, either sympatholytic drug, alone, abolished the pressor responses in the diabetes insipidus rats. This indicates that in intact conscious rats the central pressor effects of angiotensin II are initiated by vasopressin release but become dependent on the sympathetic nervous system when vasopressin is absent or not effective. When rats were allowed to drink in response to angiotensin II, a further sharp rise in blood pressure occurred, together with increases in heart rate and splanchnic nerve activity. The results demonstrate fundamental differences in the mechanisms by which central pressor peptides can influence cardiovascular and autonomic function. It is conceivable that the distinct sympathetic response patterns to central angiotensin II and substance P receptor stimulation form part of a specific cardiovascular adjustment to the individual behavioral reactions, such as drinking, as in the case of angiotensin II, or arousal within the central processing of pain, as in the case of substance P.
 ...
PMID:Differential effects of central angiotensin II and substance P on sympathetic nerve activity in conscious rats. Implications for cardiovascular adaptation to behavioral responses. 257 49

The effects of three substance P (SP) antagonists on the inferior mesenteric ganglion of the guinea-pig were studied using intracellular recording techniques, and the possible role of SP as a transmitter for the non-cholinergic slow excitatory post-synaptic potential (e.p.s.p.) was examined. The SP antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP, exerted a depolarizing action on the ganglion cells when applied by perfusion at a concentration of 3-16 microM or by pressure ejection from a micropipette. This depolarizing action is probably due to a release of endogenous histamine because it was abolished by treatment with a histamine antagonist, mepyramine (1-3 microM), or by a repeated application of the antagonist. When applied by pressure ejection, SP at 0.5-1 microM depolarized the ganglion cells. In the presence of mepyramine, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP suppressed the SP-induced depolarization by 41% at a concentration of 8 microM and by 75% at 16 microM. By contrast the SP antagonist did not affect the depolarizing action of angiotensin II on the ganglion cells. The non-cholinergic slow e.p.s.p. evoked in the ganglion cells by repetitive stimulation of the lumbar splanchnic nerves was suppressed by [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP at 8 or 16 microM. The degrees of suppression of both the non-cholinergic slow e.p.s.p. and the SP-induced depolarization by the SP antagonist were approximately equal. The cholinergic fast e.p.s.p. evoked by preganglionic nerve stimulation was not affected by the SP antagonist. [D-Pro2, D-Trp7,9]SP exhibited the properties of an SP antagonist similar to, but slightly weaker than [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP. [D-Pro2, D-Phe7, D-Trp9] at a concentration of 16 microM had a depolarizing action on the ganglion cells, which was not blocked by mepyramine. The peptide exerted hardly any antagonistic action against the SP-induced depolarization of the ganglion cells. Stimulation of the other preganglionic (intermesenteric) nerves and the post-ganglionic (colonic and hypogastric) nerves produced a non-cholinergic slow e.p.s.p. in the inferior mesenteric ganglion cells. The non-cholinergic slow e.p.s.p. evoked by both pre- and post-ganglionic nerve stimulation were depressed by [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP to similar extents. The present results show that [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP and [D-Pro2, D-Trp7,9]SP can serve as specific SP antagonists in the inferior mesenteric ganglion of the guinea-pig.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Blockade of slow excitatory post-synaptic potential by substance P antagonists in guinea-pig sympathetic ganglia. 258 Sep 73

A variety of peptides (corticotropin releasing factor (= CRF), cholecystokinin-derived peptides, neurotensin, bombesin, angiotensin II, bradykinin and substance P) induce a contraction of the myenteric plexus/longitudinal muscle preparation of the guinea-pig ileum. This excitatory effect is rapid in onset and disappears within a few minutes in the continued presence of the peptide. A part of the contractile response is antagonized by atropine indicating that acetylcholine (ACh) is involved in this effect. Following cessation of the peptide-induced contraction, a second contractile response can be elicited by the opioid antagonist naloxone. The magnitude of this naloxone induced contraction is related to the "atropine-sensitive" component of the initial contractory effect of the peptides. It appears that the peptidergic excitatory action on the plexus which is associated with release of ACh, initiates the release of opioid peptides in this tissue.
 ...
PMID:Excitatory neuropeptides activate opioid mechanisms in the guinea pig ileum. 258 5

A kinin-potentiating peptide (KPP) generated from human plasma proteins on trypsin incubation was partially purified by ultrafiltration and ion-exchange chromatography and was characterized through some of its pharmacological properties. KPP itself was devoid of any action but it potentiated the guinea-pig ileum contractions elicited by several kinins, including an analog resistant to angiotensin-converting enzyme (ACE). In contrast, contractions induced by angiotensin II, histamine, acetylcholine, barium chloride and substance P were not potentiated. Not only did KPP have high specificity towards kinins, but its action started immediately and induced kinin potentiation in a dose-dependent and reversible manner. Furthermore KPP potentiated the bradykinin contracting effects on the rat uterus, a preparation with very poor ACE activity, and on guinea-pig ileum previously incubated with 1.10-phenanthroline, a metal chelator able to inhibit ACE and kininase I activities and with phosphoramidon, a specific inhibitor of neutral endopeptidase (NEP). The results suggest that the potentiating effect of KPP is due to a mechanism different from the inhibition of kinin metabolism by ACE, NEP and kininase I.
 ...
PMID:Pharmacological properties of a new kinin-potentiating peptide generated from human serum proteins. 260 51


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