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)

Adrenal medullary cells produce not only the catecholamines norepinephrine and epinephrine but also a number of peptides; hence, they can be subclassified according to their peptide quality. The present study was an attempt to test whether different stressors address different subclasses of adrenal medullary cells. The adrenal gland of intact male rats was implanted with a dialysis system, and the jugular vein was catheterized. One day after surgery, the adrenal dialysis system was connected to a perfusion pump, and Ringer solution was used for dialysis; dialysate fractions were collected at 15-min intervals, and blood was withdrawn at the end of each fraction period after a 2-h equilibration period. The basal release rates of pituitary PRL and adrenal corticosterone, measured in plasma, and of epinephrine, norepinephrine, and substance P (SP) measured in the adrenal dialysates, were constant during the preshock period. SP concentrations in the blood were below the detection limit of the RIA. Application of mild electric foot shock stress resulted in a marked increase in adrenal catecholamine and SP release. Plasma PRL and corticosterone levels also rose during the time of exposure to foot shock, but plasma SP concentrations remained at undetectable values. In contrast, a metabolic stress i.e. insulin-induced hypoglycemia, did not affect adrenal SP release, although adrenal catecholamine release increased to a larger degree than after foot shock stress. Plasma PRL and corticosterone levels also increased during insulin-induced hypoglycemia. It is concluded that an exogenous stressor (electric foot shock) activates adrenomedullary cells containing catecholamines and SP, whereas these cells are not activated by the stress of insulin-induced hypoglycemia.
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PMID:Differential response of substance P-containing subtypes of adrenomedullary cells to different stressors. 245 51

The substances stimulating the release of immunoreactive corticotropin-releasing factor from cultured human placental cells were investigated. Monolayer primary cultures of trophoblast cells from pregnant women at term were used. The immunoreactive corticotropin-releasing factor released in the culture medium eluted from high-performance liquid chromatography with the same retention time as human corticotropin-releasing factor. Norepinephrine and acetylcholine increased immunoreactive corticotropin-releasing factor release into the culture medium in a dose-related manner. Epinephrine was partially active, whereas dopamine and serotonin did not induce significant changes of immunoreactive corticotropin-releasing factor release from placental cultures. Angiotensin II, interleukin-1, oxytocin, and arginine-vasopressin also increased placental immunoreactive corticotropin-releasing factor release in a dose-related manner, whereas other peptides (vasoactive intestinal peptide, substance P, somatostatin, atrial natriuretic factor, interleukin-2) were ineffective. These results showed that several neurotransmitters and peptides stimulate the release of immunoreactive corticotropin-releasing factor from placental cells, suggesting their possible involvement in the physiologic regulation of placental immunoreactive corticotropin-releasing factor release during pregnancy and parturition.
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PMID:Neurotransmitters and peptides modulate the release of immunoreactive corticotropin-releasing factor from cultured human placental cells. 256 97

Specific binding sites for vasoactive intestinal polypeptide (VIP) were characterized in dispersed rat parotid acini. The binding of [125I]VIP was rapid, saturable, reversible, and temperature dependent. Scatchard analysis indicated two functionally independent classes of receptor sites: 41,000 high affinity-low capacity sites per cell with a dissociation constant (Kd) of 6.4 nM and 420,000 low affinity-high capacity sites per cell with a Kd of 150 nM. A peptide with N-terminal histidine and C-terminal isoleucine and secretin, which are structurally related to VIP, inhibited the tracer binding 30 and 200 times less strongly, respectively, than VIP. Epinephrine and carbachol did not inhibit [125I]VIP binding to parotid acinar cells. VIP stimulated cAMP accumulation in parotid lobules and induced amylase secretion in a dose-dependent manner. A peptide with N-terminal histidine and C-terminal isoleucine and secretin were less potent than VIP regarding cAMP accumulation (1/12 and 1/80 of VIP, respectively) and amylase secretion (1/40 and 1/500 of VIP, respectively). Substance P did not stimulate cAMP accumulation but stimulated amylase secretion more strongly than VIP. These observations clearly demonstrated the presence of VIP receptors coupled to adenylate cyclase system in the rat parotid gland, which plays an important role in the regulation of the amylase secretion. The regulation of parotid function by VIP was independent of the adrenergic or muscarinic regulatory system and of the influence of substance P.
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PMID:Vasoactive intestinal peptide binding to specific receptors on rat parotid acinar cells induces amylase secretion accompanied by intracellular accumulation of cyclic adenosine 3'-5'-monophosphate. 257 85

The immediate response of the rabbit eye to noxious stimulation is mediated neurogenically through antidromic sensory activation and subsequent action of neuropeptides, CGRP, and substance P or a related tachykinin. The rise in ocular tension and breakdown in the BAB in response to injury are initiated by dilation and increased permeability of the ciliary vessels, which bring about disruptive alterations in the squamous epithelium covering the anterior part of the iridial processes and ciliary ridge. PGs formed during the response to certain types of irritation can enhance the ocular changes to trauma by facilitating the neurogenic pathway. In the rabbit eye substance P acts as a strong miotic in response to injury but has no effect on the IOP rise or disruption of the BAB. Conversely, CGRP is a potent vasodilator that displays no spasmogenic action. Species differences in the ocular response to injury have been observed, with lower mammals such as rabbit and rat generally being more responsive than higher mammals. For the most part, these differences are related to the organization of the iris-ciliary complex and to the sensitivity of the effector elements to the neuromediators. Reciprocal modulation exists between the autonomic and sensory nervous elements and the tissue they innervate, so that altered sensitivity of the effector cells develops in selectively denervated eyes. Chronic sympathetic denervation causes hypersensitivity of the eye to irritation. This increase is owing largely to hypertrophied sensory elements with increased sensory neuropeptide levels and consequently augmented sensory activity. Conversely, chronic sensory denervation is accompanied by an increase in catecholamine-forming enzymes and in the neuropeptide NPY. Future research will no doubt reveal neuromodulation of homeostatic, inflammatory, and vegetative processes and the ability of ocular tissues to recover from wounding. Both the discovery of biogenic neuropeptides in peripheral nervous elements of the eye alongside the classical transmitters and the elucidation of their profound effects on the eye afford scope for the development of potential new therapeutic agents.
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PMID:Mediation of the ocular response to injury and irritation: peptides versus prostaglandins. 267 45

Sialoadenectomized and sham-operated rats were given salivary secretory stimulants 30 min prior to intragastric instillation of a bile salt solution (5 mM-sodium taurocholate in 100 mM-HCl). Administration of the alpha-agonist phenylephrine (0.15-15 mg/kg) resulted in a dose-dependent reduction in the loss of H+ and the intraluminal appearance of Na+ and K+ associated with bile-salt-induced damage to the stomach in the sham-sialoadenectomized rat. The effect was not apparent if the salivary glands had been previously excised. Adrenaline (0.8-4.0 mg/kg) and noradrenaline (0.8-4.0 mg/kg) were less effective in reducing the degree of mucosal damage in sham-sialoadenectomized rats and were not effective in sialoadenectomized rats. Administration of secretory stimulant doses of isoprenaline (5 mg/kg), pilocarpine (2 mg/kg) and substance P (25 mg/kg) either had no significant effect or exacerbated the net transmucosal fluxes of H+, Na+ and K+ associated with bile salt damage to the gastric mucosa. The protective action of phenylephrine in sham-sialoadenectomized rats was reversed by prior treatment with the alpha-antagonist, phentolamine (2 mg/kg). The effect of phentolamine was dose dependent. Vagotomy abolished the protective influence of phenylephrine in sham-sialoadenectomized rats but did not influence the response to other salivary secretory stimulants consistently. These data suggest that stimulation of alpha-adrenergic receptors in rat salivary tissue is associated with an amelioration of the increase in gastric mucosal permeability to H+, Na+ and K+ in response to an intraluminal bile salt solution. The apparent protective influence of alpha-adrenergic receptor activation in sham-sialoadenectomized rats is mediated in part by the vagus nerve.
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PMID:The effect of adrenergic, cholinergic and peptidergic salivary stimulants on gastric mucosal integrity in the rat. 288 55

Epinephrine, substance P, and glutamate have all been hypothesized as primary chemical mediators in the descending pathway from the brain stem "vasomotor center" to SPNs. Interestingly, lesions of or antagonists to epinephrine, substance P, glutamate, and 5-HT neurons all abolish sympathetic activity and reduce blood pressure to a level similar to that in a spinal-transected animal. However, it is unlikely that all these substances are primary mediators of sympathetic information carried from the brain stem to the spinal cord. How then do we resolve these findings? A plausible explanation is that monoamines and neuropeptides act in the IML, as in other areas of the central nervous system, as neuromodulators, setting the level of excitability of SPNs rather than relaying sympathetic information over a functionally specific pathway from brain stem sympathetic neurons to the IML. For example, the time course of the norepinephrine-mediated slow EPSPs and IPSPs in SPNs is consistent with a gain-setting function. Likewise, the depolarization of SPNs by 5-HT is similar to the depolarization elicited in myenteric and celiac ganglion cells. In these ganglia, 5-HT appears to mediate a slow excitatory potential that enhances incoming fast synaptic potentials. A similar gain-enhancing effect of 5-HT has been demonstrated in facial motoneurons. By analogy, epinephrine is likely to act as a neuromodulator in the IML rather than to serve as the primary mediator of sympathetic information descending from the brain stem. Similarly, it is difficult to imagine that an agent with such a long duration of excitatory action as substance P could serve as the primary descending transmitter in a system where moment to moment changes in activity are essential. It is more likely that substance P aids in setting the excitability of SPNs. Pharmacological antagonism of any of the excitatory neuromodulators (i.e. gain setters) might act to decrease, at least temporarily, the excitability of SPNs to the point where primary sympathetic activity from the brain stem could not excite SPNs. This accounts for the wide variety of pharmacological agents that act to eliminate sympathetic activity and drastically reduce blood pressure. On the basis of the above arguments, the most logical candidate for a transmitter mediating primary excitatory sympathetic information from brain stem "vasomotor centers" would be an excitatory amino acid. Fast EPSPs in SPNs appear to be mediated by glutamate and excitatory amino acid antagonists markedly inhibit sympathetic activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of putative neurotransmitters on sympathetic preganglionic neurons. 289 28

Calcitonin gene-related peptide (CGRP) has recently been demonstrated in sensory neurons of the eye. The purpose of the present study was to determine the effects of exogenous CGRP in the rabbit and cat eye. CGRP was injected intracamerally and the intraocular pressure was measured in cannulated eyes. The pupil diameter and the aqueous humor protein concentration were also measured. Indomethacin was used to prevent prostaglandin synthesis and tetrodotoxin (TTX) to block nerve conductance. In the rabbit eye, CGRP caused iridial hyperemia, a breakdown of the blood-aqueous barrier and increased intraocular pressure. These responses were dose-related. The increase in IOP as well as the breakdown of the blood-aqueous barrier could not be blocked with TTX or indomethacin. In cats CGRP caused a decrease in IOP and had only slight effect on the aqueous humor protein concentration. Neither in rabbits nor in cats had CGRP any detectable effect on the pupil size. Intracameral injection of 0.1 microgram (7.4 x 10(-11) moles) substance P together with 0.1 microgram (2.6 x 10(-11) moles) CGRP in rabbits caused maximal miosis but did not potentiate the intraocular effects of CGRP only. These results indicate that CGRP has marked vascular effects in the rabbit eye, causing a breakdown of the blood-aqueous barrier and increased IOP. The mechanism of this phenomenon does not involve prostaglandins neither nerve conduction, implying most likely a direct effect on the vascular smooth muscle. The mechanism of the decrease of IOP in cats remains unknown.
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PMID:Effects of calcitonin gene-related peptide in the eye. A study in rabbits and cats. 326 93

The metabolism of phosphatidate in rat parotid acinar cells was investigated, particularly with regard to the actions of agonists known to act by mobilizing Ca2+. When cells were incubated in medium containing 10 microM-[32P]Pi, phosphatidate was rapidly labelled, approaching an apparent steady-state with a half-time of approx. 20 min. Methacholine provoked a more than doubling of phosphatidate radioactivity, which was reversed by the muscarinic antagonist atropine. These results suggest that phosphatidate labels to near steady-state rapidly and that in cells prelabelled for 60 min the increase in radioactivity induced by agonists probably reflects net synthesis rather than an increase in specific radioactivity. Phosphatidate synthesis in response to methacholine was rapid and occurred, within the resolution of a few seconds, with no measurable latency. Adrenaline and substance P also stimulated phosphatidate synthesis but both agonists were less efficacious than methacholine. A Ca2+ ionophore, ionomycin, did not provoke phosphatidate synthesis. By using a protocol that eliminates the receptor-regulated Ca2+ pool, it was demonstrated that methacholine-induced phosphatidate formation does not come about as a consequence of Ca2+ influx nor of Ca2+ release. These results indicate that the phosphatidate synthesis response has characteristics compatible with its previously suggested role as a primary mediator of membrane Ca2+-gating.
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PMID:Regulation of phosphatidate synthesis by secretagogues in parotid acinar cells. 618 Jul 40

The metabolism of phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] in rat parotid acinar cells was investigated, particularly with regard to the effects of receptor-active agonists. Stimulation of cholinergic-muscarinic receptors with methacholine provoked a rapid disappearance of 40--50% of [32P]PtdIns(4,5)P2, but had no effect on PtdIns4P. Adrenaline, acting on alpha-adrenoceptors, and Substance P also stimulated net loss of PtdIns(4,5)P2. The beta-adrenoceptor agonist, isoprenaline, and the Ca2+ ionophore, ionomycin, failed to affect labelled PtdIns(4,5)P2 or PtdIns4P. By chelation of extracellular Ca2+ with excess EGTA, and by an experimental protocol that eliminates cellular Ca2+ release, it was demonstrated that the agonist-induced decrease in PtdIns(4,5)P2 is independent of both Ca2+ influx and Ca2+ release. These results may suggest that net PtdIns(4,5)P2 breakdown is an early event in the stimulus-response pathway of the parotid acinar cell and could be directly involved in the mechanism of agonist-induced Ca2+ release from the plasma membrane.
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PMID:Receptor-mediated net breakdown of phosphatidylinositol 4,5-bisphosphate in parotid acinar cells. 618 51

Nasal vascular and airflow resistances have been measured in dogs, simultaneously on both sides separately. Vascular resistance was measured either by constant flow perfusion of the terminal branch of the maxillary artery (which supplies, via the sphenopalatine artery, the nasal septum, most of the turbinates and the nasal sinuses) or by measuring blood flow through this artery, maintained by the dog's own blood pressure. Airflow resistance was assessed by inserting balloon-tipped endotracheal catheters into the back of each nasal cavity via the nasopharynx, and measuring transnasal pressure at constant airflow through each side of the nose simultaneously. Preliminary experiments indicated that there was 5-10% collateral anastomosis between the two sides. Close-arterial injection of drugs showed different patterns of response. Adrenaline, phenylephrine, chlorpheniramine and low doses of prostaglandin F2 alpha increased vascular resistance and lowered airway resistance. Salbutamol, methacholine and histamine lowered vascular resistance and increased airway resistance. Dobutamine decreased airway resistance with a small increase in vascular resistance. Prostaglandins E1, E2 and F2 alpha (high dose) decreased both vascular and airway resistances. Substance P, eledoisin-related peptide and vasoactive intestinal polypeptide lowered vascular resistance with little change in airway resistance. The results are interpreted in terms of possible drug actions on precapillary resistance vessels, sinusoids and venules, and arteriovenous anastomoses. It is concluded that nasal airway resistance cannot be correlated with vascular resistance or blood flow, since the latter has a complex and ill-defined relationship with nasal vascular blood volume.
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PMID:Control of nasal vasculature and airflow resistance in the dog. 620 40

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