Renal adenosine A3 receptors in the rat: assessment of functional role

2000 ◽  
Vol 78 (5) ◽  
pp. 428-432 ◽  
Author(s):  
Mahmood S Mozaffari ◽  
Worku Abebe ◽  
Brett K Warren
Keyword(s):  
Rat Kidney ◽  
Acute Administration ◽  
Receptor Antagonists ◽  
Conscious Rat ◽  
Excretory Function ◽  
Functional Roles ◽  
Physiological Conditions ◽  
Key Words Adenosine ◽  
Adenosine Antagonist ◽  
First Time

The functional roles of adenosine A3 receptors in the rat kidney were assessed for the first time with respect to A1 receptor-mediated responses. Utilizing a chronically instrumented conscious rat preparation, we tested renal excretory responses to acute administration of the A3 receptor antagonists 3-ethyl - 5-benzyl-2-methyl-6-phenyl- 4-phenylethynyl-1,4-(+)-dihydropridine-3,5-dicarboxylate (MRS-1191) and 9-chloro-2-(2-furyl)-5-phenylacetylamino- [1,2,4]-triazolo[1,5-c]quinazoline (MRS-1220) with reference to the effects of the A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The intravenous administration of DPCPX resulted in significant increases in fluid and sodium excretions without affecting glomerular filtration rate (GFR). This suggests that DPCPX-induced diuretic and natriuretic responses are related to decreased tubular reabsorption. However, neither MRS-1191 nor MRS-1220 alone affected fluid or sodium excretions, or GFR, indicating lack of an effect of either compound on renal function. On the other hand, the co-administration of MRS-1220 with DPCPX abolished both the diuretic and natriuretic responses to DPCPX, being suggestive of antagonism between these two compounds. MRS-1191, however, did not affect the DPCPX-induced fluid and sodium excretions. Neither the A1 nor the A3 receptor antagonists altered potassium excretion individually or in combination. The data suggest that while adenosine A1 receptors are involved in the regulation of renal fluid and sodium transport, A3 receptors do not appear to have a major role in regulation of renal excretory function under baseline physiological conditions. Key words: adenosine A3 receptor, adenosine antagonist, diuresis, natriuresis, rat.

scholarly journals Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model

2021 ◽  
Vol 22 (5) ◽  
pp. 2479
Author(s):  
Amir Mohammadzadeh ◽  
Péter P. Lakatos ◽  
Mihály Balogh ◽  
Ferenc Zádor ◽  
Dávid Árpád Karádi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Animal Studies ◽  
Acute Administration ◽  
Pain Model ◽  
Therapeutic Value ◽  
Small Doses ◽  
Function Test ◽  
Neuropathic Pain Model ◽  
First Time ◽  
Glycine Content

The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.

Generation of angiotensin II from human plasma by tissue kallikrein

1992 ◽  
Vol 83 (4) ◽  
pp. 477-482 ◽  
Author(s):  
N. Krivoy ◽  
H. Schlüter ◽  
M. Karas ◽  
W. Zidek
Keyword(s):  
Angiotensin Ii ◽  
Molecular Mass ◽  
Human Plasma ◽  
Rat Kidney ◽  
Ionization Mass ◽  
Tissue Kallikrein ◽  
Porcine Pancreas ◽  
Physiological Conditions ◽  
Perfused Rat Kidney ◽  
Vasopressor Activity

1. Human plasma was incubated with tissue kallikrein from porcine pancreas, dialysed to obtain a fraction with a molecular mass < 10 kDa and further purified by reverse-phase chromatography. 2. Vasopressor activity in the fractions obtained was tested in the isolated perfused rat kidney. 3. In one fraction a strong vasopressor action was found, which was blocked by saralasin and by an angiotensin II antibody. 4. Aprotinin inhibited the formation of vasopressor substances by tissue kallikrein. 5. U.v.-laser desorption/ionization mass spectrometry revealed a molecular mass of 1046 Da in the purified active fraction. 6. It is concluded that tissue kallikrein forms not only kinins, but also angiotensin II, from human plasma under physiological conditions.

scholarly journals Sigma-1 receptor antagonists haloperidol and chlorpromazine modulate the effect of glutoxim on NA+ transport in frog skin

2019 ◽  
Vol 484 (5) ◽  
pp. 629-632
Author(s):  
Z. I. Krutetskaya ◽  
A. V. Melnitskaya ◽  
V. G. Antonov ◽  
A. D. Nozdrachev
Keyword(s):  
Voltage Clamp ◽  
Frog Skin ◽  
Na Transport ◽  
Receptor Antagonists ◽  
Sigma 1 Receptor ◽  
Voltage Clamp Technique ◽  
Frog Skin Epithelium ◽  
Sigma 1 ◽  
Immunomodulatory Drug ◽  
First Time

Using voltage-clamp technique, the involvement of sigma-1 receptors in immunomodulatory drug glutoxim regulation of Na+ transport in frog skin was investigated. We have shown for the first time that preincubation of the frog skin with sigma-1 receptor antagonists – haloperidol or chlorpromazine – attenuates the stimulatory effect of glutoxim on Na+ transport. The results suggest the possible involvement of the sigma-1 receptors in glutoxim effect on Na+transport in frog skin epithelium.

Stimulation of the Parapyramidal Region of the Neonatal Rat Brain Stem Produces Locomotor-Like Activity Involving Spinal 5-HT7 and 5-HT2A Receptors

2005 ◽  
Vol 94 (2) ◽  
pp. 1392-1404 ◽  
Author(s):  
Jun Liu ◽  
Larry M. Jordan
Keyword(s):  
Brain Stem ◽  
Pattern Generator ◽  
Neonatal Rat ◽  
Cycle Duration ◽  
Receptor Antagonists ◽  
Step Cycle ◽  
Output Stage ◽  
Discrete Population ◽  
First Time ◽  
Neonatal Rat Brain

Locomotion can be induced in rodents by direct application 5-hydroxytryptamine (5-HT) onto the spinal cord. Previous studies suggest important roles for 5-HT7 and 5-HT2A receptors in the locomotor effects of 5-HT. Here we show for the first time that activation of a discrete population of 5-HT neurons in the rodent brain stem produces locomotion and that the evoked locomotion requires 5-HT7 and 5-HT2A receptors. Cells localized in the parapyramidal region (PPR) of the mid-medulla produced locomotor-like activity as a result of either electrical or chemical stimulation, and PPR-evoked locomotor-like activity was blocked by antagonists to 5-HT2A and 5-HT7 receptors located on separate populations of neurons concentrated in different rostro-caudal regions. 5-HT7 receptor antagonists blocked locomotor-like activity when applied above the L3 segment; 5-HT2A receptor antagonists blocked locomotor-like activity only when applied below the L2 segment. 5-HT7 receptor antagonists decreased step cycle duration, consistent with an action on neurons involved in the rhythm-generating function of the central pattern generator (CPG) for locomotion. 5-HT2A antagonists reduced the amplitude of ventral root activity with only small effects on step cycle duration, suggesting an action directly on cells involved in the output stage of the pattern generator for locomotion, including motoneurons and premotor cells. Experiments with selective antagonists show that dopaminergic (D1, D2) and noradrenergic (α1, α2) receptors are not critical for PPR-evoked locomotor-like activity.

Colleters in the vegetative axis of Aechmea blanchetiana (Bromeliaceae): anatomical, ultrastructural and functional aspects

2018 ◽  
Vol 66 (5) ◽  
pp. 379 ◽  
Author(s):  
Igor Ballego-Campos ◽  
Elder Antônio Sousa Paiva
Keyword(s):  
Developmental Stages ◽  
Light And Electron Microscopy ◽  
Secretory Activity ◽  
Functional Roles ◽  
Reproductive Axis ◽  
Functional Aspects ◽  
The Family ◽  
Marginal Cells ◽  
First Time

Colleters are common among eudicotyledons, but few records exist for monocotyledons and other groups of plants. For Bromeliaceae, mucilage secretions that protect the young portions of the plant have been observed only in the reproductive axis, and little is known about the secretory systems behind this or even other kind of secretions in the family. We aimed to describe, for the first time, the occurrence of colleters associated with the vegetative shoot of Aechmea blanchetiana (Baker) L.B.Sm., and elucidate aspects of their structure, ultrastructure and secretory activity. Samples of various portions of the stem axis were prepared according to standard methods for light and electron microscopy. Colleters were found compressed in the axillary portion of leaves and in all leaf developmental stages. Secretory activity, however, was found to be restricted to young and unexpanded leaves. The colleters displayed a flattened hand-like shape formed by a multiseriate stalk and an expanded secretory portion bearing elongated marginal cells. Ultrastructural data confirmed that the secretory role of the colleters is consistent with mucilaginous secretion. The functional roles of the colleters are discussed with regard to environmental context and intrinsic features of the plant, such as the presence of a water-impounding tank.

Glomerular blood flow after single nephron obstruction in the rat kidney

1986 ◽  
Vol 250 (1) ◽  
pp. F77-F85 ◽  
Author(s):  
G. A. Tanner ◽  
L. C. Knopp
Keyword(s):  
Blood Flow ◽  
Castor Oil ◽  
Enzyme Inhibitor ◽  
Rat Kidney ◽  
Chronic Administration ◽  
Acute Administration ◽  
Tubule Lumen ◽  
Single Nephron ◽  
Micron Diameter ◽  
High Doses

This study examined the effects of kidney tubule lumen obstruction on glomerular blood flow (GBF) in anesthetized rats. GBF was estimated using microspheres having 9 micron diameter and averaged 239 +/- 10 nl/min in normal nephrons of 41 control rats. Tubule blockade with either paraffin wax or castor oil produced identical results. GBF after 1-2 h of obstruction did not differ from normal. After 1 day, GBF averaged two-thirds of normal, and after 1 wk GBF averaged one-third of normal. The hemodynamic changes produced by obstruction for 1 wk were diminished by chronic administration of high doses of the converting enzyme inhibitor captopril or acute administration of the angiotensin antagonist saralasin. The results suggest that angiotensin contributes to the vasoconstriction produced by prolonged obstruction. Nephrons blocked with castor oil contained oil 1 wk later, had a GBF of 88 +/- 24 nl/min, and were atrophied. We conclude that chronic single nephron obstruction produces progressive vasoconstriction, that this response is in part angiotensin mediated, and that the end result is nephron atrophy.

Changes in mRNAs for enzymes of glutamine metabolism in kidney and liver during ammonium chloride acidosis

1994 ◽  
Vol 267 (3) ◽  
pp. F400-F406 ◽  
Author(s):  
A. C. Schoolwerth ◽  
P. A. deBoer ◽  
A. F. Moorman ◽  
W. H. Lamers
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Kidney ◽  
Glutamine Metabolism ◽  
Kidney Cortex ◽  
Mrna Levels ◽  
Rat Kidney Cortex ◽  
Physiological Conditions ◽  
Glutamine Synthase ◽  
Sustained Increase

Changes in protein and mRNAs for enzymes of glutamine metabolism were determined in rat kidney cortex at different times after induction of NH4Cl acidosis. After NH4Cl, phosphoenolpyruvate carboxykinase (PEPCK) mRNA increased 16-fold by 10 h (P < 0.05) and then returned to control levels by 30 h. In situ hybridization (ISH) showed that PEPCK mRNA was confined to medullary rays; after NH4Cl, expression of PEPCK expanded throughout the cortex, reaching a maximal intensity at 10 h. Phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase (GDH) mRNAs increased 8- and 2.6-fold, respectively (both P < 0.05), by 10 h before decreasing; the increased expression was confirmed by ISH. Immunohistochemistry showed that increased PEPCK, PDG, and GDH protein occurred at variable times after the rise in mRNAs. The increase was confined to proximal tubules and was sustained, a finding noted also by Western blot analysis. In contrast, glutamine synthase protein and mRNA, confined to deep cortex and outer medullar, did not change after NH4Cl. These studies reveal striking changes in PEPCK and PDG mRNAs in rat renal cortex during acidosis. The ISH pattern suggested that increased amounts of PEPCK were synthesized in recruited cells which contained little enzyme under physiological conditions. mRNA levels for PEPCK, PDG, and GDH peaked at 10 h before returning to control levels. Despite the decrease in mRNAs, a sustained increase in proteins was noted.

scholarly journals BTCI enhances guanylin-induced natriuresis and promotes renal glomerular and tubular effects

2008 ◽  
Vol 68 (1) ◽  
pp. 149-154 ◽  
Author(s):  
AF. Carvalho ◽  
MS. Santos-Neto ◽  
HSA. Monteiro ◽  
SM. Freitas ◽  
L. Morhy ◽  
...  
Keyword(s):  
Filtration Rate ◽  
Rat Kidney ◽  
Structural Features ◽  
Urine Flow ◽  
Renal Metabolism ◽  
Chymotrypsin Inhibitor ◽  
Electrolyte Homeostasis ◽  
Perfused Rat Kidney ◽  
First Time

Guanylin and uroguanylin are small cysteine-rich peptides involved in the regulation of fluid and electrolyte homeostasis through binding and activation of guanylyl cyclases signaling molecules expressed in intestine and kidney. Guanylin is less potent than uroguanylin as a natriuretic agent and is degraded in vitro by chymotrypsin due to unique structural features in the bioactive moiety of the peptide. Thus, the aim of this study was to verify whether or not guanylin is degraded by chymotrypsin-like proteases present in the kidney brush-border membranes. The isolated perfused rat kidney assay was used in this regard. Guanylin (0.2 µM) induced no changes in kidney function. However, when pretreated by the black-eyed pea trypsin and chymotrypsin inhibitor (BTCI - 1.0 µM; guanylin - 0.2 µM) it promoted increases in urine flow (deltaUF of 0.25 ± 0.09 mL.g-1/min, P < 0.05) and Na+ excretion (% delta ENa+ of 18.20 ± 2.17, P < 0.05). BTCI (1.0 µM) also increased %ENa+ (from 22.8 ± 1.30 to 34.4 ± 3.48, P < 0.05, 90 minutes). Furthermore, BTCI (3.0 µM) induced increases in glomerular filtration rate (GFR; from 0.96 ± 0.02 to 1.28 0.02 mL.g-1/min, P < 0.05, 60 minutes). The present paper strongly suggests that chymotrypsin-like proteases play a role in renal metabolism of guanylin and describes for the first time renal effects induced by a member of the Bowman-Birk family of protease inhibitors.

Relationship between basal NO release and cyclooxygenase products in the normal rat kidney

1996 ◽  
Vol 271 (5) ◽  
pp. R1327-R1334 ◽  
Author(s):  
C. Baylis ◽  
B. Slangen ◽  
S. Hussain ◽  
C. Weaver
Keyword(s):  
Renal Function ◽  
Pressor Response ◽  
Rat Kidney ◽  
High Dose ◽  
Conscious Rat ◽  
Physiological Regulation ◽  
Renal Vasoconstriction ◽  
No Inhibition ◽  
Normal Rat ◽  
Renal Hypoperfusion

We investigated the physiological regulation of renal function by nitric oxide (NO) and its interactions with the endothelial cyclooxygenase products in the conscious, chronically catheterized rat. A subpressor dose of NO inhibitor nitro-L-arginine methyl ester (L-NAME) produced renal vasoconstriction that was unaffected by cyclooxygenase inhibition with indomethacin (Indo). Acute, high-dose L-NAME produced a pressor response of approximately 40 mmHg and marked renal vasoconstriction. Indo selectively amplified the renal vasoconstriction, whereas inhibition of the thromboxane-endoperoxide receptor had no effect. Chronic NO inhibition for 5 wk led to sustained hypertension and renal vasoconstriction; the latter was amplified by acute Indo. These data suggest that in the normal, conscious rat the kidney is under important NO-dependent tone. There is no obvious interaction between NO and the cyclooxygenase products in control of basal renal function. When systemic NO inhibition is produced with either acute or chronic high-dose L-NAME, the kidney is severely vasoconstricted. The renal vasoconstriction is not ameliorated by thromboxane-endoperoxide antagonism but is exacerbated by cyclooxygenase blockade, suggesting that vasodilator cyclooxygenase products compensate for the renal hypoperfusion because of severe NO deficiency.

scholarly journals In Vivo Reconstitution of γ-Secretase in Drosophila Results in Substrate Specificity

2010 ◽  
Vol 30 (13) ◽  
pp. 3165-3175 ◽  
Author(s):  
Denise Stempfle ◽  
Ritu Kanwar ◽  
Alexander Loewer ◽  
Mark E. Fortini ◽  
Gunter Merdes
Keyword(s):  
Cell Culture ◽  
Cellular Differentiation ◽  
Biochemical Properties ◽  
Notch Receptor ◽  
Aspartyl Protease ◽  
Physiological Conditions ◽  
Functional Differences ◽  
Specific Factors ◽  
First Time

ABSTRACT The intramembrane aspartyl protease γ-secretase plays a fundamental role in several signaling pathways involved in cellular differentiation and has been linked with a variety of human diseases, including Alzheimer's disease. Here, we describe a transgenic Drosophila model for in vivo-reconstituted γ-secretase, based on expression of epitope-tagged versions of the four core γ-secretase components, Presenilin, Nicastrin, Aph-1, and Pen-2. In agreement with previous cell culture and yeast studies, coexpression of these four components promotes the efficient assembly of mature, proteolytically active γ-secretase. We demonstrate that in vivo-reconstituted γ-secretase has biochemical properties and a subcellular distribution resembling those of endogenous γ-secretase. However, analysis of the cleavage of alternative substrates in transgenic-fly assays revealed unexpected functional differences in the activity of reconstituted γ-secretase toward different substrates, including markedly reduced cleavage of some APP family members compared to cleavage of the Notch receptor. These findings indicate that in vivo under physiological conditions, additional factors differentially modulate the activity of γ-secretase toward its substrates. Thus, our approach for the first time demonstrates the overall functionality of reconstituted γ-secretase in a multicellular organism and the requirement for substrate-specific factors for efficient in vivo cleavage of certain substrates.

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