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 present study was aimed at investigating which tachykinin receptor subtypes mediate the inhibitory effects of tachykinins a) on salt intake induced by sodium depletion, b) on water intake induced by subcutaneous hypertonic NaCl administration and c) on water intake induced by central angiotensin II injection. The study was carried out by evaluating the potency of action, following intracerebroventricular injection, of several peptides, including both naturally occurring tachykinins and synthetic peptides selective for a given receptor subtype. The results obtained show different rank orders of potency of the agonists in the different behavioral tests, thus suggesting that different receptor subtypes are involved in the effects of tachykinins on water and salt intake. NK-3 receptors appear to be involved in the inhibitory effect of tachykinins on depletion-induced salt appetite. NK-2 receptors apparently mediate the inhibitory effect of tachykinins on drinking induced by hyperosmotic NaCl administration, while NK-1 receptors are probably involved in the inhibition of angiotensin II-induced drinking.
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PMID:Tachykinin receptor subtypes involved in the central effects of tachykinins on water and salt intake. 184 83

Three types of binding sites for the mammalian tachykinins, ie Substance P (SP) Neurokinin A (NKA) and Neurokinin B (NKB), have been found in both the central and peripheral nervous systems. Substance P binds to the NK-1 subclass of binding site while NKA and NKB are less selective endogenous ligands, which preferentially interact with the NK-2 and NK-3 subclasses of binding sites, respectively. Complementary strategies, including 3-dimensional structure analysis by NMR spectroscopy and structure-activity relationship led to the design of selective agonists of these binding sites. [Pro9] SP, [Pro10] SP and the cyclic analogues [Cys3,6, Tyr8, Pro9] SP and [Cys3,6, Tyr8, Pro10] SP are selective NK-1 agonists. [Lys5] NKA(4-10) is a water soluble NK-2 potent agonist. Finally, [Pro7] NKB, which completely discriminates NK-2 and NK-3 binding sites, is a water-soluble NK-3 selective agonist.
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PMID:Selective agonists of tachykinin binding sites. 216 64

In the guinea-pig isolated, perfused lung, the effect of albumin on oedema formation and bronchoconstriction as well as on capsaicin-induced overflow of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity has been examined. CGRP was used as an indicator of sensory nerve activation since it is more stable than the tachykinins substance P and neurokinin A. As expected, the lung water content was significantly (P less than 0.001) higher in lungs perfused with albumin-free buffer than when the buffer contained 4.5% albumin. Also, in albumin-free buffer the baseline airway resistance (RL) was increased and dynamic compliance (CDYN) reduced (P less than 0.001). Capsaicin (1 x 10(-6) M) was about 100 times less potent as a bronchoconstrictor when preincubated with albumin for 45 min, and the associated overflow of CGRP-LI was inhibited (from 221.0 +/- 63.4 fmol to 8 fmol fraction-1). When CGRP (50-200 pM) was incubated for 60 min with albumin, the recovery of CGRP-LI was 48% lower (P less than 0.01) than in the absence of albumin, corresponding to a loss rate of about 1% min-1. Catabolism or binding of neuropeptides can therefore hardly explain the diminished bronchoconstrictor potency of capsaicin. Capsaicin was also less effective as a constrictor in isolated bronchi after preincubation with albumin, suggesting that capsaicin itself may be bound or absorbed to this macromolecule. The bronchoconstrictor response to adenosine was also diminished in the presence of albumin. Adenosine was about 1000 times less potent as a bronchoconstrictor if dissolved in albumin 45 min before infusion, but only 10 times less potent when administered as bolus doses to albumin buffer-perfused lungs. Metabolism of adenosine may be the reason for the decreased potency of adenosine. The enzymatic activity may have been associated with impurities in the albumin preparation used (bovine serum albumin fraction V is greater than or equal to 96% pure) or contained in the protein itself. Since the bronchoconstrictor effect of acetylcholine was not reduced in the presence of albumin, it is not likely that albumin affects directly the contractility of the smooth muscle. These data demonstrate the importance of studying the influence of albumin on the in-vitro actions of pharmacological agents. The absence or presence of albumin products in nutrient buffer solutions may mean dramatic differences in potencies of certain drugs. Furthermore, bolus injections of agents are preferable, and preincubation together with albumin should be avoided.
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PMID:Albumin protects against capsaicin- and adenosine-induced bronchoconstriction and reduces overflow of calcitonin gene-related peptide from guinea-pig lung. 219 39

Central administration of the tachykinins, eledoisin or physalaemin has been reported to produce significant water intake in pigeons but inhibition of stimulated drinking in rats. In this paper it is shown that high and low doses of these two tachykinins injected centrally in two much larger species, goats and pigs, did not produce any significant drinking. Furthermore, in pigs, physalaemin, but not eledoisin, attenuated AII stimulated drinking (576 +/- 64 ml AII alone, versus 456 +/- 131 ml AII + eledoisin, not significant, and 124 +/- 89 ml AII plus physalaemin, p less than 0.01, in the same 5 pigs) and also, especially at the higher doses, induced general locomotor activation. However, in goats neither tachykinin interfered with drinking induced by central injection of 300 ng AII. These results show that in pigs and goats the tachykinins, eledoisin and physalaemin, are not effective dipsogens and that one of the possible reasons for the inhibitory action of physalaemin on AII-induced drinking may be through the general locomotor activation and not through a direct effect on the central AII system.
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PMID:Effect of central tachykinins, alone and with angiotensin II, on drinking in pigs and goats. 220

This study investigated the sensitivity of spontaneously hypertensive rats (SHR) and of Wistar Kyoto rats (WKR) to the antidipsogenic action of the tachykinin eledoisin (ELE). Drinking was evoked by: (a) intracerebroventricular (i.c.v.) injection of angiotensin II, (b) subcutaneous (s.c.) administration of hypertonic NaCl (1.5 M; 1 ml/100 g b.wt.) or (c) 18 h of water deprivation with free access to food. In accordance with previous studies, the dipsogenic effect of all three treatments was exaggerated in the SHR. And when treated with i.c.v. ELE (12.5-25 ng/rat) they were far less sensitive than WKR to its antidipsogenic action on angiotensin-induced drinking. Smaller differences in strain sensitivity were also observed for the effect of ELE on cell dehydration- and on water deprivation-induced drinking, but only at the dose of 200 and 50 ng/rat, respectively. The different sensitivity of the SHR to the antidipsogenic effect of ELE supports the idea that tachykininergic mechanisms for control of water intake are differently regulated in the SHR than they are in the normotensive WKR.
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PMID:Sensitivity of spontaneously hypertensive and of Wistar Kyoto rats to the antidipsogenic action of eledoisin. 232 4

The present study reports the effects of ICV administered eledoisin, the most potent anti/dipsogenic member of the tachykinin family, in three species. Sheep with chronic parotid fistula lost daily 200-400 mmol sodium in 3-4 l of saliva. During ICV infusion of eledoisin, 2 to 50 ng/min, a decrease in sodium intake was observed. If water was withheld for 22 hours, sheep normally drank 5.4 l water on presentation. During ICV infusion of eledoisin, 50 ng/min, water intake increased significantly. Wild rabbits lost 5 mmol sodium in 50 ml of urine after injection of furosemide. During ICV infusion of eledoisin, 30 ng/min, a decrease in sodium intake and an increase in water drinking was observed. Cows prepared with parotid fistula had access to sodium solution every other day to replace salivary sodium loss. During ICV infusion of eledoisin, 50 and 150 ng/min, a decrease in sodium intake occurred, and water intake was unaffected. These results confirm that central administration of eledoisin specifically influences ingestive behaviour in mammals and draws attention to some species differences in the observed effects.
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PMID:Sodium and water intake of sheep, rabbits and cattle during ICV infusion of eledoisin. 234 60

Sodium-replete pigeons drink excess 3% NaCl following concurrent treatment with both i.m. deoxycorticosterone acetate and pulse i.c.v. (p.i.c.v.) angiotensin II. This is not just a consequence of the water intake induced by p.i.c.v. angiotensin II, since the tachykinin eledoisin, given at equidipsogenic dose, does not evoke intake of salt. On the other hand, salt intake is not aroused in the sodium replete pigeon by continuous i.c.v. (c.i.c.v.) infusion of hyperosmotic mannitol (0.7 M) and c.i.c.v. infusions of hyperosmotic NaCl (0.3 M) or mannitol have no effect on the salt intake of the sodium deplete pigeon, or have effects that are unrelated to brain sodium. The salt appetite of the pigeon, like that of the rat, is evoked by an angiotensin and aldosterone synergy, and the angiotensin/aldosterone mechanism may be the general vertebrate theme of this behavior.
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PMID:Angiotensin/aldosterone synergy governs the salt appetite of the pigeon. 236 14

The undecapeptide substance P (SP) is contained in enterochromaffin cells and circulates in high concentrations in patients with carcinoid syndrome. We have previously reported that elevated SP levels, simulating those reported in patients with carcinoid syndrome, induce profound changes in intestinal water and electrolyte secretion, motility, and blood flow in a canine model. The purpose of this study was to attempt to block the effects of circulating carcinoid levels of SP on intestinal secretion and motility with the calcium channel blocker verapamil. In five dogs a chronic proximal jejunal Thiry-Vella loop was constructed, and after a 2-week recovery the loops were perfused with an isotonic test solution containing 14C-polyethylene glycol as a volume marker. Motor activity was measured by changes in intraluminal pressure and a motility index was calculated with computer-assisted planimetry and expressed as square millimeters per 5 minutes. After a 30-minute baseline period, SP was infused at 50 ng/kg/min for 90 minutes. SP circulating levels rose from a baseline of 6.2 +/- 1.3 pg/ml to a peak of 93.3 +/- 3.1 pg/ml during this infusion. Thirty minutes after the start of this SP infusion, a simultaneous infusion of verapamil (5.0 micrograms/kg/min) was begun at a separate site. During SP infusion there was a significant secretory response of water (-48 +/- 12 microliters/min), Na+ (-7.7 +/- 2.5 microEq/min), Cl- (-8.8 +/- 2.7 microEq/min) and K+ (-0.57 +/- 0.14 microEq/min), and hypermotility (motility index: 1479 +/- 138 mm2/5 min). When verapamil was added a reversal of secretion to net absorption was observed (water: + 116.9 +/- 15.6 microliter/min; Na+: + 13.8 +/- 2.1 microEq/min; Cl-: + 5.5 +/- 2 microEq/min; K+: + 0.38 +/- 0.9 microEq/min) (p less than 0.05). In addition, there was a reduction in motility (motility index: 853 +/- 92 mm2/5 min; p less than 0.05). These results confirm that SP has profound effects on both intestinal motility and secretion and that calcium channel blockade reduces these effects significantly.
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PMID:Verapamil inhibition of the intestinal effects of substance P. 241 Sep 86

The enterochromaffin (EC) cell system is distributed throughout the entire gastrointestinal tract. Enterochromaffin cells are the major source of intestinal serotonin (5-HT), but separate subpopulations of EC cells may synthesize and store peptides as substance P (SP), motilin, and enkephalin as well. Of special interest is that 5-HT and SP, which may coexist in EC cells, have several functional similarities, i.e., inhibition of gastric acid secretion, stimulation of intestinal motility, and secretion of water and electrolytes. Carcinoid tumors are derived from the gut endocrine system. Depending on site of origin, carcinoids are divided into foregut, midgut, and hindgut derivatives with different clinical symptoms. A common biochemical feature of midgut carcinoids is the production of 5-HT and SP. Histochemically, midgut carcinoids are characterized by the argentaffin reaction--a direct reduction of silver salts owing to 5-HT. Specific antisera for the immunocytochemical demonstration of secretory products are available as well. Despite their relative infrequency, carcinoids are the most common small intestinal tumors. The common appendix tumors generally have a benign clinical course, whereas the small intestinal tumors have different growth patterns and frequently metastasize with increasing size, and may thus give rise to the carcinoid syndrome (diarrhea, facial flush, right-sided cardiac valvular disease, and asthma). Carcinoid symptoms first appear when hepatic inactivation of 5-HT is exceeded, unless the carcinoid has an extraintestinal localization, for example, ovarian lesions may elicit symptoms in the absence of hepatic disease owing to direct secretion into systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin and carcinoid tumors. 241 66

The effects of thyroid and gonadal status on the content of substance P in the anterior pituitary (AP-SP) were examined in prepubertal rats. A sex difference in AP-SP is evident by age 50 days [males, 287 +/- 35 fmol/mg protein (mean +/- SE); females, 103 +/- 17; P less than 0.05], and this difference becomes greater by 75 days (males, 543 +/- 54; females, 146 +/- 11.5; P less than 0.01). Hypothyroidism was induced in male and female pups by giving lactating dams 0.1% methimazole (wt/vol) in their drinking water after parturition. There was a marked and significant increase in AP-SP in 21-day-old hypothyroid compared to euthyroid control pups. Male pups were made thyrotoxic by daily treatment with T4 (10 micrograms/rat, sc) from age 8 to 15 days. AP-SP was 4 times lower in the thyrotoxic than in the euthyroid pups (P less than 0.001). Rats ovariectomized at age 22 days and killed on day 35 revealed no change in AP-SP, in contrast to the rise in AP-SP in the ovariectomized adult rat. Female pups were treated with dihydrotestosterone (DHT; 50 micrograms/day) or testosterone (50 micrograms/day) from age 8-20 days. Neither androgen induced a change in AP-SP. Female pups which received estradiol (E2; 0.5 micrograms/day) or testosterone (75 micrograms/day) from age 8-20 days also had no change in AP-SP. As opposed to the lack of effect of E2 and DHT on AP-SP in female rats younger than 22 days, E2 (1 microgram/100 g BW daily) caused a decrease and DHT (100 micrograms/100 g BW daily) caused an increase in AP-SP in female rats treated from 22-35 days of age [E2, 91 +/- 6.9; DHT, 226 +/- 31 (P less than 0.05 vs. control for both); control, 154 +/- 13]. We conclude that the responsiveness of AP-SP to alterations in thyroid status is present at the youngest age studied. In contrast, the responsiveness of AP-SP to changes in the levels of gonadal steroids is absent in the infantile period and requires a maturational process that becomes evident during the juvenile state of sexual development.
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PMID:The differential effects of thyroid and gonadal hormones on substance P content in the anterior pituitary of the prepubertal rat. 241 5


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