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 mechanisms of action of tachykinin peptides thought to be involved in central cardiovascular regulation were examined. Intracerebroventricular injections (i.c.v.) of tachykinin peptides caused dose-dependent increases in blood pressure and heart rate. The pressor responses to substance P (SP) (10 micrograms, i.c.v.) and neurokinin A (NKA) (10 micrograms, i.c.v.) were blocked by peripheral administration of pentolinium or phentolamine, and partially attenuated by adrenalectomy. In contrast, the only initial pressor response to the neurokinin B (NKB) analogue senktide (10 micrograms, i.c.v.) was blocked by pentolinium or phentolamine. The pressor response to senktide was inhibited by pretreatment with a vasopressin V1 receptor antagonist (d(CH2)5OMe(Tyr)AVP) (10 micrograms/kg, i.v.), and senktide (10 micrograms, i.c.v.) caused an increase in plasma vasopressin level. However, the vasopressin antagonist did not influence the SP- and NKA-induced pressor responses. These results suggest that central SP and NKA increase the blood pressure and heart rate via sympathetic nerve activity, whereas central NKB increases the blood pressure mainly via release of vasopressin from the hypothalamus.
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PMID:Role of central tachykinin peptides in cardiovascular regulation in rats. 170 26

Brains, retrocerebral complexes and frontal and suboesophageal ganglia of adult American cockroaches, Periplaneta americana, were immunohistochemically investigated with a specific monoclonal antibody (McAb) directed against a well characterized antigenic determinant, namely the COOH terminus of the endecapeptide substance P (SP). This resulted in the detection of several neurons and nerve fibres containing a substance antigenically closely related to this typically vertebrate neuropeptide. No difference in staining pattern could be observed between male and female insects. Related to the age of the adult specimens, however, a slight quantitative difference in SP immunoreactivity seems to occur, which probably might have functional implications. The SP-like peptide demonstrated in this study appears to be located in different neuronal structures than the ones that we earlier described as containing ACTH-, CRF-, OT-, AVP-, NP I-, NP II-, BPP-, FMRFamide-, AKH-, met-ENK-, FSH-, LH- and LHRF-like material (Verhaert et al. 1984a, b, 1985; Verhaert and De Loof 1985a, b).
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PMID:Substance P-like immunoreactivity in the central nervous system of the blattarian insect Periplaneta americana L. revealed by a monoclonal antibody. 241 98

The microcirculatory effects of vasoactive peptides on arteriolar diameter were determined in the dorsal skin-fold preparation of conscious Syrian hamsters and related to arterial blood pressure (MABP). (5 Ile)-angiotensin II (ANG II), (8 Arg)-vasopressin (AVP), vasoactive intestinal polypeptide (VIP), atrial natriuretic factor (ANF), and substance P (SP) were administered intravenously as bolus injections in picomolar concentrations. The diameters of subcutaneous A3 arterioles (15-40 microns) at bifurcation sites were determined via a microscope video system and stored in a digital memory. When spontaneous rhythmic vasoconstrictions and dilations (vasomotion) were present, the diameter oscillations were analyzed by means of the Prony Spectral Line Estimator. ANG II caused sustained arteriolar contraction at increased MABP, but did neither induce nor modulate vasomotion. Both ANF and VIP slightly reduced MABP and had no effect on microcirculatory parameters. SP led to a significant dilation of subcutaneous arterioles in the hamster skin with concomitant drop in MABP, but did not influence arteriolar vasomotion. Physiological concentrations of AVP, as determined in the plasma by radioimmunoassay, caused a marked contraction of the arterioles and evoked a mild pressor response. In addition, AVP induced or greatly enhanced vasomotoric activity. This study therefore provides evidence that endogenous vasoactive peptides play an important role in regulation of skin peripheral resistance by altering arteriolar diameter in a tonic or even dynamic way.
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PMID:Regulatory role of vasoactive peptides in subcutaneous skin microcirculation of the hamster. 245 Aug 51

Characterization of specific vasopressin binding sites was investigated in purified mouse Leydig cells using tritiated arginine-vasopressin. Binding of radioligand was saturable, time- and temperature-dependent and reversible. (3H)-AVP was found to bind to a single class of sites with high affinity (Kd = 2.20 +/- 0.18 nM) and low capacity (Bmax = 17.4 +/- 1.8 fmol/10(6) Leydig cells). Binding displacements with specific selective analogs of AVP indicated the presence of V1 subtype receptors on Leydig cells. The ability of AVP to displace (3H)-AVP binding was greater than LVP and oxytocin. The unrelated peptides, somatostatin and substance P, were less potent, while neurotensin and LHRH did not displace (3H)-AVP binding. The time-course effects of AVP-pretreatment on basal and hCG-stimulated testosterone and cAMP accumulations were studied in primary culture of Leydig cells. Basal testosterone accumulation was significantly increased by a 24 h AVP-pretreatment of Leydig cells (P less than 0.001). This effect was potentiated by the phosphodiesterase inhibitor (MIX) and was concomitantly accompanied by a slight but significant increase in cAMP accumulation (P less than 0.01). AVP-pretreatment of the cells for 72 h had no effect on basal testosterone accumulation, but exerted a marked inhibitory effect on the hCG-stimulated testosterone accumulation (P less than 0.001). This reduction of testosterone accumulation occurred even in the presence of MIX and was not accompanied by any significant change of cAMP levels. We conclude from these data that AVP is capable of modulating steroidogenesis in Leydig cells through specific and functionally V1 receptor subtype and postulate that this effect may be part of an intratesticular paracrine/autocrine control mechanism.
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PMID:Modulation of mouse Leydig cell steroidogenesis through a specific arginine-vasopressin receptor. 245 54

Neurons with intrinsic pacemaker activity and presumed sympathoexcitatory function were recorded in rat tissue slices within the confines of the rostroventrolateral reticular nucleus (RVL). These cells were excited in dose-dependent fashion by arginine vasopressin (AVP, 10(8)-10(6) M) but not by oxytocin (up to 10(7) M). The effect of AVP was mimicked by the V1-selective agonist [Phe2,Orn8]vasotocin (VT) (1 microM) but not by the V2-agonist [Val4,D-Arg8]vasopressin (VP) (1.9 microM). The effect of AVP (10(-7) M) was completely blocked by SKF 101926 (10(7) M), a non-selective antagonist and by d(CH2)5[Tyr(Me)2]AVP, a V1-selective antagonist but was unaffected by the V2-selective antagonist d(CH2)5[D-Ile2,Ile4,Ala-NH2 9]AVP. These cells were also activated by thyrotropin-releasing hormone (TRH) (10(-7)-10(-6) M), calcitonin gene-related peptide (CGRP) (4 X 10(-8) M), substance P, (10(-6) M), neuropeptide Y (NPY) (10(-8) M) and inhibited by Met-enkephalin (10(-6) M) and morphine (2 mM). Corticotropin-releasing factor (CRF) (10(-7) M) and angiotensin II (10(-6) M) were ineffective. In conclusion, RVL pacemaker neurons have vasopressin receptors reminiscent of the V1 (vascular and pressor) subtype. Their pacemaking activity is modulated by low doses of several other peptides also known to produce large vasomotor effects after introduction into the cerebroventricular space.
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PMID:Effects of vasopressin and other neuropeptides on rostral medullary sympathoexcitatory neurons 'in vitro'. 275

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
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PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87

Intracerebroventricular (i.c.v.) injections of senktide (0.01-10 nmol), a tachykinin NK-3 agonist, had an antidiuretic action in water-loaded rats (4.5% body wt.). Pretreatment with OPC-31260 (1 mg/kg, i.v.), a non-peptide vasopressin V2 antagonist, inhibited the antidiuretic action induced by exogenous arginine vasopressin (AVP, 0.1 micrograms/kg, i.v.) and senktide (0.1 nmol, i.c.v.). In addition, senktide (11.8 nmol, i.c.v.) caused a marked increase of the plasma AVP level in conscious rats. These results suggest that the central NKB analogue senktide has an antidiuretic effect by stimulating AVP secretion from the pituitary gland through the NK-3 receptor in the hypothalamus.
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PMID:Central administration of senktide, a tachykinin NK-3 agonist, has an antidiuretic action by stimulating AVP release in water-loaded rats. 750 13

1. Primary afferent neurones releasing the vasodilator, calcitonin gene-related peptide, mediate the gastric hyperaemic response to acid back-diffusion. The tachykinins neurokinin A (NKA) and substance P (SP) are located in the same neurones and are co-released with calcitonin gene-related peptide. In this study we investigated the effect and possible role of tachykinins in the acid-evoked gastric vasodilatation in urethane-anaesthetized rats. 2. Gastric acid back-diffusion, induced by perfusing the stomach with 15% ethanol in the presence of 0.05 M HCl, increased gastric mucosal blood flow by 60-90%, as determined by the hydrogen clearance technique. NKA and SP (0.14-3.78 nmol min-1 kg-1, infused intra-aortically) inhibited the gastric mucosal hyperaemic response to acid back-diffusion in a dose-dependent manner, an effect that was accompanied by aggravation of ethanol/acid-induced macroscopic haemorrhagic lesions. 3. The inhibitory effect of NKA (1.26 nmol min-1 kg-1) on the acid-induced gastric mucosal vasodilatation was prevented by the tachykinin NK2 receptor antagonists, MEN 10,627 (200 nmol kg-1) but left unaltered by the NK1 receptor antagonist, SR 140,333 (300 nmol kg-1) and the mast-cell stabilizer, ketotifen (4.6 mumol kg-1). 4. Under basal conditions, with 0.05 M HCl being perfused through the stomach, NKA (1.26 nmol min-1 kg-1) reduced gastric mucosal blood flow by about 25%, an effect that was abolished by SR 140,333 but not MEN 10,627 or ketotifen. 5. SR 140,333, MEN 10,627 or ketotifen had no significant effect on basal gastric mucosal blood flow nor did they modify the gastric mucosal hyperaemic reaction to acid back-diffusion. 6. The effect of NKA (1.26 nmol min-1 kg-1) in causing vasoconstriction and inhibiting the vasodilator response to acid back-diffusion was also seen when blood flow in the left gastric artery was measured with the ultrasonic transit time shift technique. 7. Arginine vasopressin (AVP, 0.1 nmol min-1 kg-1) induced gastric mucosal vasoconstriction under basal conditions but was unable to inhibit the dilator response to acid back-diffusion. 8. These data show that NKA has two fundamentally different effects on the gastric circulation. Firstly, NKA reduces gastric blood flow by activation of NK1 receptors. Secondly, NKA inhibits the gastric hyperaemic response to acid back-diffusion through an NK2 receptor-mediated mechanism. These two tachykinin effects appear to take place independently of each other since they are mediated by different receptors. This concept is further supported by the inability of AVP to mimic tachykinin inhibition of the gastric vasodilator response to acid back-diffusion.
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PMID:Tachykinin inhibition of acid-induced gastric hyperaemia in the rat. 898 97

Mammalian pineal gland receives peptidergic (e.g., vasoactive intestinal peptide [VIP]; peptide histidine isoleucine [PHI]; neuropeptide Y, NPY; substance P, calcitonin gene-related peptide [CGRP], arginine vasopressin [AVP] and oxytocin [OXT]) fibers in addition to sympathetic innervation. The dynamics of cAMP efflux and melatonin (MT) secretion were compared during the infusion of these peptides in our long-term perifusion system. VIP and PHI enhanced both pineal cAMP efflux and MT secretion in a dose-dependent manner (10 nM to 10 microM). However, the potency of PHI was slightly less. The peak of cAMP release always precedes that of MT production. The possible interactions between adrenergic and peptidergic compounds in the regulation of pineal cAMP efflux and MT secretion were also studied. VIP acts on specific peptidergic receptors, since its stimulatory effect could only be reduced by a VIP receptor antagonist. VIP has an additive effect at a lower (100 nM) concentration combined with norepinephrine (NE). NPY (100 nM) can completely block NE-induced MT secretion, but the decrease in cAMP efflux is less. However, NPY does not significantly influence VIP-stimulated cAMP efflux or MT secretion. These data suggest that NE, VIP, and NPY are differently involved in the cAMP and calcium signaling. The other neuropeptides are ineffective.
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PMID:Adrenergic and peptidergic control of the regulation of cAMP efflux and melatonin secretion from perifused rat pineal gland. 979 35

The aim of the present investigations was to study the influence of substance P (a member of a family of peptides known as tachykinins) on basal and K(+)-evoked vasopressin (AVP) and oxytocin (OT) release from rat hypothalamo-neurohypophysial system in vitro as well as to determine whether this effect of substance P is sensitive to melatonin. The present results show that substance P stimulates basal AVP and OT release from isolated hypothalamo-neurohypophysial system, when used at the concentrations of 10(-6) and 10(-7)M/l. At the concentration of 10(-9)M/l, however, substance P was found to stimulate the in vitro secretion of AVP, but not that of OT. Melatonin diminished basal release of AVP; it also significantly inhibited the substance P-stimulated secretion of AVP and OT. K(+)-evoked release of the neurohypophysial hormones was not further modified by either substance P or melatonin. The present results show that the stimulatory effect of substance P on basal release of AVP and OT from rat hypothalamo-neurohypophysial system in vitro is sensitive to inhibitory influence of melatonin.
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PMID:Melatonin inhibits the substance P-induced secretion of vasopressin and oxytocin from the rat hypothalamo-neurohypophysial system: in vitro studies. 1250 91


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