UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regularly discharging baroreceptors in a rat in vitro aortic arch preparation were exposed to increasing concentrations of one of four vasoactive peptides: angiotensin II, arginine vasopressin, atrial natriuretic factor, or substance P. Slow ramps of pressure evoked discharge responses in single-fiber baroreceptors. Instantaneous discharge frequency was measured simultaneously with aortic diameter and pressure. During constriction induced by angiotensin II or arginine vasopressin, baroreceptor diameter threshold (Dth) decreased and pressure threshold (Pth) tended to increase; these effects were reduced or eliminated by nitroprusside. Atrial natriuretic factor and substance P by themselves were without effect on vessel diameter or on baroreceptor discharge. In preparations preconstricted with a moderate concentration of phenylephrine (10(-8) M), atrial natriuretic factor reduced the phenylephrine-induced constriction and increased Dth and decreased Pth. Substance P, even at high concentrations, was less effective than atrial natriuretic factor in reducing phenylephrine constriction and in altering baroreceptor discharge. Baroreceptor gain was unaffected by any of these peptides. Thus, changes in smooth muscle tone altered mechanotransduction by shifts in 1) the vessel pressure-diameter relation and 2) baroreceptor threshold requirements (Pth and Dth). Changes in the baroreceptor mechanical threshold (Dth) reduced the effects on Pth expected from changes in vessel wall mechanics. Pth reflects the net effects of vessel wall and Dth changes. Pth generally increased during constrictions and decreased during dilations. The changes in Dth and their selectivity (no changes in gain) during vasoactive peptide action closely resemble rapid resetting of baroreceptors. We propose that vascular smooth muscle lies in a parallel arrangement with aortic baroreceptors and that a common compensatory mechanism regulates Dth during sustained changes in vessel diameter. Activation of smooth muscle and reductions in transmural pressure would reduce loading of baroreceptors, and the proposed compensatory mechanism would tend to keep discharge constant by decreasing Dth. Our experiments, however, cannot distinguish between hypotheses for local micromechanical changes in coupling or for changes modulating excitability within the baroreceptor neuron itself as the basis for Dth adjustments.
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PMID:Peptidergic modulation of mechanotransduction in rat arterial baroreceptors. 168 17

The present study tested whether release of dopamine from isolated bovine adrenal medullary cells in culture could be stimulated or inhibited by secretagogues and modulators known to affect noradrenaline and adrenaline release from adrenal medullary chromaffin cells. K+ depolarization or activation of voltage-sensitive Na+ channels by veratridine both stimulated dopamine release. Ca2+-dependent dopamine release was also stimulated by the mixed nicotinic-muscarinic agonist, carbachol. Carbachol-induced dopamine release was inhibited by a nicotinic but not by a muscarinic antagonist and dopamine release was also stimulated by a selective nicotinic agonist, 1,1-dimethyl-4-phenyl-piperazinium. Carbachol-induced dopamine release was inhibited by substance P and by neuropeptide Y. Histamine also stimulated dopamine release, while angiotensin II and glutamate produced no significant stimulation of dopamine release. Noradrenaline and adrenaline were released in response to the above agents with a profile almost identical to that of dopamine. The results indicate that dopamine can be directly released from adrenal medullary cells in response to stimulation of those cells and suggest that the dopamine release originates from chromaffin cells similar or identical to those storing noradrenaline and adrenaline. A possible role for dopamine, released from adrenal chromaffin cells, in modulating catecholamine release from the chromaffin cells and/or contributing to circulating plasma dopamine is discussed.
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PMID:Dopamine release from bovine adrenal medullary cells in culture. 169 90

The present study investigated the sensitivity of the medial region of the amygdala to the antinatriorexic action in the rat of the tachykinins eledoisin, substance P, neurokinin A and [Asp5,6, MePhe8] substance P(5-11) (also referred to as amino-senktide; NH2-SENK), which is a highly selective agonist for NK-3 receptors. The results obtained show that only the potent NK-3 agonists eledoisin and NH2-SENK inhibit salt appetite when injected into the medial region of the amygdala. Eledoisin and NH2-SENK inhibited salt appetite induced by sodium depletion, that has been proven to be governed by the synergism of angiotensin and aldosterone. They inhibited also salt appetite evoked by central renin injection, that is due to production of angiotensin II. On the other hand, eledoisin and NH2-SENK did not inhibit salt appetite evoked by subcutaneous deoxycorticosterone treatment. These findings suggest that the medial region of the amygdala is a site of action for the antinatriorexic effect of tachykinins and that their action at this site is mediated by NK-3 receptors. Moreover, our results show that in the medial amygdala, the antinatriorexic action of tachykinins appears to be directed toward the angiotensinergic component of the neural mechanism for salt appetite.
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PMID:Inhibition of salt appetite in the rat following injection of tachykinins into the medial amygdala. 169 38

The discovery of peptides in the splanchnic nerve and adrenal gland, and their co-existence with conventional neurotransmitters raises questions about their possible functional roles in catecholamine (CA) secretion and gene transcription in the adrenal gland. Short-term, stress-induced CA secretion is regulated biphasically by substance P (SP) which inhibits acetylcholine (ACh) action at SP greater than 10(-6) M and facilitates CA secretion in response to metabolic and physical stressors, ACh or electrical stimulation at SP less than 10(-6) M. Long-term, gene transcription of phenylethanolamine-N-methyltransferase (PNMT) is exerted by glucocorticoids, and gene transcription of Proenkephalin-A by agents such as histamine, angiotensin II and VIP that increase cyclic AMP (cAMP). The final products of these two genes, adrenaline and Met-enkephalin and congeners, are co-stored in chromaffin granules of adrenaline cells but gene expression of these products is clearly under differential control.
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PMID:Peptide regulation of adrenal medullary function. 169 30

The antihypertensive effect of inhibitors of the angiotensin I-converting enzyme (ACE = kininase II) results from their vasodilatory and natriuretic effects as well as their effect on baroreceptor function. In addition to the inhibition of systemic and local angiotensin II formation, other local hormonal systems may also be involved in this effect at multiple target sites. Thus, potentiation of the vasodilator and natriuretic kinin system following inhibition of kininase II is thought to contribute to the persistent hypotensive effect of ACE inhibitors despite normalization of circulating ACE activity. Although increased plasma bradykinin levels cannot be detected, we found that the enhanced kinin-dependent local vascular prostacyclin production can be blunted in vitro by aprotinin, a kallikrein inhibitor. ACE inhibition may affect the atrial natriuretic peptide (ANP) system as the renin-angiotensin system and ANP appear to play antagonistic roles at the peripheral and central nervous system levels. Inhibition of kallikrein or of kininase II were both shown to modulate the natriuretic and vasorelaxant effects of ANP. In hypertensive subjects, we found that ACE inhibition with blood pressure normalization reduces basal and stimulated plasma ANP and blunts the renal sodium excretion in response to saline loading. In contrast, we did not observe effects of acute ACE inhibition in healthy sodium-depleted volunteers on plasma vasopressin under basal conditions or in response to passive tilt. Finally, we investigated the interaction of ACE inhibition with substance P, a powerful endogenous diuretic and natriuretic peptide that may have a transmitter function in the baroreceptor reflex arch.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinin- and non-kinin-mediated interactions of converting enzyme inhibitors with vasoactive hormones. 169 69

Cardiovascular responses to intracerebroventricular (icv) injections of substance P and somatostatin were measured in Long-Evans and Brattleboro rats treated with streptozotocin (STZ) or saline. Substance P icv evoked similar pressor responses and tachycardia in STZ-treated and saline-treated Long-Evans rats, together with signs of behavioral activation (i.e., arousal). As a group, Brattleboro rats did not respond significantly to icv substance P, although some individual rats showed clear cardiovascular and behavioral responses. These findings may indicate a reduced sensitivity to icv substance P in Brattleboro rats but show no differences attributable to STZ treatment. Hence, diminished pressor responses to icv angiotensin II (observed previously) may be specific to sympathoadrenal activation associated with drinking. Somatostatin caused a pressor effect in saline-treated, but not in STZ-treated, Long-Evans rats, which was probably due to arginine vasopressin (AVP)-mediated mechanisms because it was not present in either saline-treated or STZ-treated Brattleboro rats. Both control and STZ-treated Long-Evans rats showed a bradycardic response to somatostatin that was not seen in Brattleboro rats. These results indicate that different AVP-mediated mechanisms might be responsible for the pressor and bradycardic effects of icv somatostatin. It is possible that impairment of central somatostatin-mediated AVP release contributes to the diminished role of AVP in blood pressure recovery following ganglion blockade in STZ-treated rats described previously.
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PMID:Central effects of substance P and somatostatin in conscious, streptozotocin-treated rats. 169 38

Binding sites for thyrotropin-releasing hormone (TRH) were labelled with [3H](2-Me-His3)TRH ([3H]MeTRH) on membranes from rat brain regions at 0 degrees C for 5 h. Amygdaloid membranes bound [3H]MeTRH with high-affinity (Kd = 3.1 +/- 0.5 nM (n = 4)). Five TRH analogs competed for this binding with the same rank order and with affinities that matched the pharmacological specificity of pituitary TRH receptors. Substance P (SP) and its C-terminal fragments reduced amygdaloid TRH receptor binding in a concentration dependent manner (IC50 for SP = 65 microM). The rank order of potency of SP analogs at inhibiting TRH receptor binding was: SP greater than nonapeptide (3-11) greater than hexapeptide (6-11) greater than heptapeptide (5-11) greater than pentapeptide (7-11). However, other tachykinins were inactive in this system. SP was a potent inhibitor of [3H]MeTRH binding in hippocampus greater than spinal cord greater than retina greater than n. accumbens greater than hypothalamus greater than amygdaloid greater than olfactory bulb greater than or equal to pituitary greater than pons/medulla in parallel assays. In amygdaloid membranes SP (50 microM) reduced the apparent maximum receptor density by 39% (p less than 0.01) without altering the binding affinity, and 100 microM SP induced a biphasic dissociation of [3H]MeTRH with kinetics faster than those induced by both TRH (10 microM) and serotonin (100 microM). In contrast, other neuropeptides such as neurotensin, proctolin, angiotensin II, bombesin and luteinizing hormone releasing hormone did not significantly inhibit [3H]MeTRH binding to amygdaloid membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A novel substance P binding site in rat brain regions modulates TRH receptor binding. 170 85

Changes in the intracellular free calcium ([Ca2+]i) of cultured normal human epidermal keratinocytes (NHEK) were investigated in order to determine whether the adenylate cyclase cAMP (AC) system and phospholipase C activating system are involved in increasing [Ca2+]i. NHEK were obtained from neonatal foreskin and grown in serum-free medium (K-GM) supplemented with 2% bovine pituitary extract. [Ca2+]i was measured by fluorescence ratio imaging microscopy using Fura-2 as the indicator. In the case of the AC system, transient increases in [Ca2+]i were observed in response to stimulation with epinephrine, norepinephrine, isoproterenol and salbutamol. Methoxamine, clonidine and dobutamine did not induce any [Ca2+]i increase. The [Ca2+]i increase evoked by epinephrine was inhibited by pretreatment with propranolol, but not by prazosin or yohimbine, indicating that epinephrine-induced [Ca2+]i elevation via beta 2-adrenergic stimulation. Similar changes were observed when NHEK were stimulated with histamine, adenosine, GTP gamma S, forskolin and dibutyryl cAMP respectively. The absence of extracellular Ca2+ had no effect on the epinephrine-induced [Ca2+]i increase. It appears that activated protein kinase A, based on cAMP accumulation via stimulatory GTP binding protein, elicited the release of Ca2+ from intracellular stores. On the other hand, when drugs known to activate phospholipase C in a wide variety of cell types were tested, a transient increase in [Ca2+]i was demonstrated in response to the addition of thrombin, bradykinin and substance P. This reaction was not affected by the presence of EGTA, suggesting that these drugs raise [Ca2+]i via phosphatidylinositol breakdown. Vasopressin, angiotensin II, serotonin and acetylcholine did not induce any increase in [Ca2+]i. On the basis of these studies, it was concluded that NHEK possess the mechanism which increase [Ca2+]i via AC system and phospholipase C activating system. It seems probable that this rise in [Ca2+]i initiates a calcium-dependent cellular response, such as activation of calcium/calmodulin dependent kinase, and subsequently regulates the proliferation and differentiation of human epidermal keratinocytes.
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PMID:[Changes in the intracellular free calcium of cultured human epidermal keratinocytes]. 171 97

1. Intragastric pressure (IGP) was used as an index, of the effect of serosal application of captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) on the contractility of rat stomach in vitro. 2. Captopril, at concentrations greater than 0.3 microM, enhanced the spontaneous gastric motility (GM) in a concentration-dependent manner whereas concentrations less than 0.3 microM selectively potentiated 4 nM bradykinin (BK)-evoked gastric contractions without significantly affecting the spontaneous GM. 3. The kallikrein inhibitor, aprotinin (100 u ml-1), markedly antagonized the enhanced GM to 1.4 microM captopril and BK (4 nM)-evoked contractions, without affecting the contractions evoked by angiotensin 1 (10 nM) and acetylcholine (0.4 microM). The angiotensin II antagonist, saralasin (50 microM) failed to mimic aprotinin. 4. The enhanced GM to captopril was markedly inhibited by tetrodotoxin (1 microM), and partially inhibited by atropine (1 microM). 5. These results indicate that in vitro, captopril (greater than 0.3 microM) enhances gastric contractility through kininase/ACE inhibitory action, presumably by increasing the concentration of undegraded tissue kinins and substance P. This motor response seems to be predominantly due to activation of the cholinergic neurones but non-cholinergic excitatory neurones are also involved.
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PMID:Enhanced contractility of the rat stomach during suppression of angiotensin converting enzyme by captopril in vitro. 171 7

The present study evaluated the effect of the intracerebroventricular injection of the tachykinins, substance P, neurokinin A and [Asp5.6,MePhe8]substance P(5-11) (also referred to as NH2-senktide), on the alcohol intake of genetically selected, alcohol-preferring rats. Animals were offered both water and 8% ethanol 2 h/day; tachykinins were administered just before access to fluids. Neurokinin A and substance P did not modify alcohol intake at doses up to 1000 and 2000 ng/rat, respectively. On the other hand, NH2-senktide potently suppressed alcohol intake at doses of 31.2-500 ng/rat. At the same doses, however, it did not significantly affect water intake. This finding suggests that its effect on alcohol intake might be rather selective and not due to general impairment of the behavior. Activation of tachykinin NK-3 receptors, for which NH2-senktide is a highly selective agonist, produces angiotensin II release in the brain; however, the effect of NH2-senktide on alcohol intake is probably not mediated by angiotensin II, as suggested by the fact that it is not modified by captopril pretreatment.
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PMID:The tachykinin NH2-senktide inhibits alcohol intake in alcohol-preferring rats. 171 9

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