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)

1. A large-conductance Cl- channel was characterized in cell-free membrane patches from the rabbit longitudinal colonic smooth muscle using the patch clamp technique. In addition, the regulation of these channels by neurokinin-1 (NK-1) receptor agonists and G proteins was studied. 2. No spontaneous channel activity was observed in cell-attached patches at the cell resting potential, or in excised patches at pipette potentials (Vp) between -20 and 20 mV. In excised patches, channel activity could be induced in thirty-six out of ninety-six patches by holding the patch at Vp values more negative than -60 mV or more positive than 60 mV. Once induced, the channel showed a bell-shaped voltage activation curve in high symmetric [Cl-], with maximal open probability between 20 and -5 mV. Varying cytosolic calcium concentration ([Ca2+]) between 5 x 10(-8) M and 1.0 mM had no effect on the voltage activation of the channel. 3. In inside-out and outside-out patches, when pipette and bath solutions contained equal [Cl-] (130 mM), the anion channel showed a linear current-voltage (I-V) relationship between -60 and 60 mV with a slope conductance of 309 +/- 20 pS (n = 13). Reversal potential measurements indicated that the channel was selective for Cl- over Na+ and K+ (PCl/PNa = 6:1). 4. Channel openings from the closed state to the full open state as well as transitions through smaller conductance states were observed. The smallest detectable substate had a conductance of 15.6 pS. Based on the similarities in selectivity and linearity of the I-V curve of the smaller conductances with the full open state, and kinetic analysis of channel activity, it is concluded that the large conductance channel is composed of multiple substates which can either open and close independently, or simultaneously via a main gate. 5. The stilbene derivative diiso-thiocyanato-stilbene-disulphonic acid (DIDS) and the diphenylamine-2-carboxylate analogue 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) caused a dose-dependent, reversible flicker block of the small conductance and significantly reduced the macroscopic current flow through the channel. 6. In quiescent outside-out patches, when the pipette contained a 140 mM-CsCl solution with 10(-6) M-CaCl2, 1.2 mM-MgCl2 and 1 mM-GTP, and the bath contained Ringer solution, addition of the NK-1 receptor antagonists substance P methylester resulted in activation of the full conductance state and of smaller substates.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Characterization of large-conductance chloride channels in rabbit colonic smooth muscle. 137 40

Immunohistochemical techniques were used to study the adrenal organs of the anuran species Rana esculenta, Caldula pulchra and Bufo marinus with respect to the distribution and coexistence of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), Leu-enkephalin (Leu-ENK). Met-enkephalin-Arg-Phe (MEAP) and dynorphin A 1-17 (DYN). Antisera against enzymes involved in catecholamine synthesis, i.e., dopamine-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), were used for the identification of chromaffin cells. ANP-immunoreactive (-IR) cells occurred in high densities (30%-70% of the total cell population) in all species investigated. In C. pulchra and B. marinus, BNP-IR cells constituted a population of non-DBH-IR and non-TH-IR cells that were different from the ANP-IR cells. A large proportion of the adrenal cells (10%-55%) were immunoreactive to Leu-ENK, and a minority (2%-5%) showed MEAP-immunoreactivity. DYN-immunoreactivity was not observed. The anurans studied exhibited small numbers of SP-IR, CGRP-IR and NPY-IR cells. Immunoreactivities for ANP + Leu-ENK and Leu-ENK + MEAP were shown to coexist. In C. pulchra and B. marinus, immunoreactions for ANP + NPY, ANP+SP and SP + CGRP were also colocalized. Except for DYN, all neurohormonal peptides also occurred in intra-adrenal nerve fibers. SP-IR fibers also displayed CGRP-immunoreactivity and some Leu-ENK-IR fibers contained MEAP-immunoreactivity. In C. pulchra, NPY-IR fibers were found that also showed ANP-immunoreactivity.
 ...
PMID:Distribution patterns and coexistence of neurohormonal peptides (ANP, BNP, NPY, SP, CGRP, enkephalins) in chromaffin cells and nerve fibers of the anuran adrenal organ. 137 3

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)
 ...
PMID:Kinin- and non-kinin-mediated interactions of converting enzyme inhibitors with vasoactive hormones. 169 69

Brain natriuretic peptide (BNP) is a recently discovered family of natriuretic peptides highly homologous to atrial natriuretic factor (ANF). Quantitative in vitro autoradiography with a computerized microdensitometer demonstrated that the distribution of BNP binding sites is similar to the known distribution pattern of ANF binding sites in rat tissues. Analysis of saturation and competition curves disclosed that the maximal binding capacity for BNP-(Asp-81--Tyr-106) and ANF-(Ser-99--Tyr-126) is similar within the plexiform layer of the olfactory bulb, the choroid plexus, and the adrenal zona glomerulosa. Examination of the competition curves of BNP-(Asp-81--Tyr-106), ANF-(Ser-99--Tyr-126), and des-(Gln-116--Gly-120)ANF-(Asp-102--Cys-121)NH2 (C-ANF, a ligand highly specific for ANF-R2 receptors) for 125I-labeled BNP-(Asp-81--Tyr-106) and 125I-labeled ANF-(Ser-99--Tyr-126) binding revealed that ANF fully displaced 125I-BNP binding and, conversely, BNP completely displaced 125I-ANF binding in these tissues, whereas C-ANF partially displaced 125-BNP and 125-ANF binding. Angiotensin II, insulin, glucagon, and substance P had no influence on 125I-BNP binding in the above tissues. These results support the view that BNP and ANF share the same binding sites in rats.
 ...
PMID:Brain natriuretic peptide binding sites in rats: in vitro autoradiographic study. 216 36

We review recent studies on the central neural control of esophageal motility, emphasizing the anatomy and chemical coding of esophageal pathways in the spinal cord and medulla. Sympathetic innervation of the proximal esophagus is derived primarily from cervical and upper thoracic paravertebral ganglia, whereas that of the lower esophageal sphincter and proximal stomach is derived from the celiac ganglion. In addition to noradrenaline, many sympathetic fibers in the esophagus contain neuropeptide Y (NPY), and both noradrenaline and NPY appear to decrease blood flow and motility. Preganglionic neurons innervating the cervical and upper thoracic ganglia are located at lower cervical and upper thoracic spinal levels. The preganglionic innervation of the celiac ganglion arises from lower thoracic spinal levels. Both acetylcholine (ACh) and enkephalin (ENK) have been localized in sympathetic preganglionic neurons, and it has been suggested that ENK acts to pre-synaptically inhibit ganglionic transmission. Spinal afferents from the esophagus are few, but have been described in lower cervical and thoracic dorsal root ganglia. A significant percentage contain calcitonin gene-related peptide (CGRP) and substance P (SP). The central distribution of spinal afferents, as well as their subsequent processing within the spinal cord, have not been addressed. Medullary afferents arise from the nodose ganglion and terminate peripherally both in myenteric ganglia, where they have been postulated to act as tension receptors, and, to a lesser extent, in more superficial layers. Centrally, these afferents appear to end in a discrete part of the nucleus of the solitary tract (NTS) termed the central subnucleus. The transmitter specificity of the majority of these afferents remains unknown. The central subnucleus, in turn, sends a dense and topographically discrete projection to esophageal motor neurons in the rostral portion of the nucleus ambiguous (NA). Both somatostatin-(SS) and ENK-related peptides have been localized in this pathway. Finally, motor neurons from the rostral NA innervate striated portions of the esophagus. In addition to ACh, these esophageal motor neurons contain CGRP, galanin (GAL), N-acetylaspartylglutamate (NAAG), and brain natriuretic peptide (BNP). The physiological effect of these peptides on esophageal motility remains unclear. Medullary control of smooth muscle portions of the esophagus have not been thoroughly investigated.
 ...
PMID:Central neural control of esophageal motility: a review. 220 57

Immunohistochemistry was used to localize brain natriuretic peptide in the porcine spinal cord and to compare it with that of atrial natriuretic peptide, substance P, calcitonin gene-related peptide and [Met]enkephalin. Brain natriuretic peptide-immunoreactive varicose fibers were observed in lamina I and the inner portion of lamina II of the dorsal horn. Semiquantitative analysis showed that the highest density of brain natriuretic peptide-immunoreactive varicosities was in the lumbosacral and coccygeal segments. The distributional pattern of brain natriuretic peptide-immunoreactive nerve fibers in the spinal cord was unique and quite distinct from that of the other neuropeptides studied. These neuroanatomical findings suggest that brain natriuretic peptide may play a role in the regulation of nociceptive processing in the spinal cord, either alone or with bioactive substances.
 ...
PMID:Brain natriuretic peptide in the porcine spinal cord: an immunohistochemical investigation of its localization and the comparison with atrial natriuretic peptide, substance P, calcitonin gene-related peptide, and enkephalin. 248 53

Aromatase in the diencephalic neurons, the level of which increases transiently during the prenatal to neonatal period, has been suggested to be involved in control of sexual behavior and differentiation of the CNS. Effects of neurotransmitters on levels of aromatase mRNA in cultured neurons were investigated to determine factors regulating the developmental increase that occurs in level of fetal brain aromatase. The expression of aromatase in diencephalic neurons of fetal mice at embryonic day 13, cultured in vitro, was significantly affected by alpha 1-adrenergic receptor ligands. Aromatase mRNA levels were higher in neurons treated with the alpha 1-agonist phenylephrine than in control neurons, whereas prazosin, an alpha 1-antagonist, suppressed this increase, and ligands for alpha 2- or beta-adrenergic receptors did not exert any influence. The profile of alpha 1-adrenergic receptor subtypes during actual development in vivo suggested that the alpha 1B subtype is in fact responsible for the signal transduction. Substance P, cholecystokinin, neurotensin, and brain natriuretic peptide also increased the level of expression along with phorbol 12-myristate 13-acetate and dibutyrylcyclic GMP, whereas forskolin and dibutyryl-cyclic AMP caused a decrease. These data indicate that stimulation via alpha 1 (possibly alpha 1B)-adrenergic receptors, as well as receptors of specific neuropeptides, controls the expression of aromatase in embryonic day 13 diencephalic neurons through activation of protein kinase C or G. beta-Adrenergic receptors would not appear to participate in the regulation, judging from their developmental profile, although cyclic AMP might be a suppressive second messenger.
 ...
PMID:Neurotransmitter-mediated regulation of brain aromatase: protein kinase C- and G-dependent induction. 886 18

1. The relaxant of vasodilator peptides were examined in ring preparations of basilar arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. 2. Vasoactive intestinal peptide and peptide histidine isoleucine produced similar endothelium-independent relaxations in basilar arteries from WKY rats and SHRSP. Calcitonin gene-related peptide (CGRP) elicited endothelium-independent relaxations in both groups and the CGRP-induced relaxation was greater in SHRSP than in WKY rats. Substance P and neurokinin A did nor relax basilar arteries from either group. 3. Both WKY rat and SHRSP basilar arteries were relatively insensitive to atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide. 4. Bradykinin (BK) potently relaxed basilar arteries with endothelium, but BK produced contractions in endothelium-rubbed arteries in both WKY rats and in SHRSP. There was no significant difference in the relaxant response to BK between WKY rat and SHRSP arteries. 5. Adrenomedullin (AM) produced endothelium-independent relaxations in both groups and the relaxant response to AM was significantly greater in SHRSP than in WKY rats. 6. Human CGRP(8-37;mumol/L), a CGRP receptor antagonist, significantly inhibited both relaxant responses induced by CGRP and AM in WKY rats and in SHRSP arteries. 7. Among various peptides tested, the responses to CGRP and AM were higher in basilar arteries from SHRSP than in those from WKY rats. The relaxation produced by AM may be via CGRP receptors in WKY rat and SHRSP basilar arteries.
 ...
PMID:Relaxant effects of vasodilator peptides on isolated basilar arteries from stroke-prone spontaneously hypertensive rats. 907 89

A transient increase in aromatase activity is known to occur in the hypothalamus of rodents in pre- and postnatal periods. The mechanisms regulating such a developmental increase of brain aromatase was studied in fetal mouse diencephalic cells, by measuring aromatase mRNA levels by a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. When slices of diencephalon were cultured on embryonic day (E) 12, E13 and E15, the level of aromatase mRNA continued to increase for the first 2 to 3 days. A time-dependent increase of mRNA was also shown for 3 days in E13 neuronal cells dissociated with papain and cultured in chemically defined medium. However, no significant increase was observed in E10 or E11 brain cells cultured by either method. Aromatase mRNA was detected in neither cerebral cortex neurons nor astrocytes. An alpha1-selective adrenergic agonist, phenylephrine, increased aromatase in the E13 diencephalic neurons in culture, whereas prazosin, an alpha1-antagonist, suppressed the mRNA level. Ligands for alpha2- or beta-adrenergic receptors did not alter the mRNA level. Substance P, cholecystokinin, neurotensin, and brain natriuretic peptide as well as phorbol 12-myristate 13-acetate and dibutyryl-cyclic GMP all increased the mRNA level. We concluded that: (a) the developmental increase of aromatase mRNA in diencephalic neurons is an autonomous event and is perhaps genetically regulated after E12; (b) aromatase mRNA is expressed in a cell type- and region-specific manner; and (c) protein kinases C and G activated via receptors of the specific neurotransmitters may be involved in modulation of the developmental expression of aromatase mRNA.
 ...
PMID:Autonomous expression of aromatase during development of mouse brain is modulated by neurotransmitters. 936 5

1. We have examined the role of extracellular chloride in the mast cell secretion process. The immunologically-directed ligand, antibody to IgE (anti-IgE) required extracellular chloride ions for optimum secretion from rat peritoneal mast cells. In contrast, replacement of extracellular chloride did not alter the mast cell secretory response to compound 48/80, calcium ionophore A23187 or substance P. 2. Anti-IgE-stimulation of mast cells evoked a significant uptake of chloride ions compared to non-stimulated cells. The magnitude of chloride uptake correlated with the magnitude of stimulated histamine secretion. 3. Compound 48/80, substance P and A23187 did not alter the rate of chloride ion uptake, although these agents caused significant histamine secretion. 4. The Na+/K+/2Cl- cotransport inhibitor, furosemide, reduced the rate of anti-IgE-stimulated chloride uptake at a relatively high concentration (700 microM). However, the more potent Na+/K+/2Cl- cotransport inhibitors, bumetanide (100 microM) and piretanide (100 microM) had no effect on the stimulated chloride uptake. 5. Furosemide inhibited anti-IgE-induced histamine secretion, bumetanide potentiated the response and piretanide had no effect. This suggests that their respective action on histamine secretion are unrelated to inhibition of the Na+/K+/2Cl- carrier. 6. The chloride channel blocker, 5-nitro-2-((3-phenylpropyl)-amino)-benzoic acid (NPPB), reduced both anti-IgE-stimulated chloride uptake and the corresponding histamine secretion in a dose-dependent manner. The magnitude of the inhibitory action of the drug on these two cellular processes was comparable, implying that chloride channel activity is related to the mechanism of histamine secretion. 7. It is concluded that chloride uptake has a role in the control of Fc epsilon RI-mediated histamine secretion from rodent mast cells.
 ...
PMID:Fc epsilon RI-mediated chloride uptake by rat mast cells: modulation by chloride transport inhibitors in relation to histamine secretion. 940 85


1 2 3 Next >>