Dose-Dependent Actions of Spironolactone on the Inner and Outer Zones of the Guinea Pig Adrenal Cortex

Pharmacology ◽  
1992 ◽  
Vol 45 (1) ◽  
pp. 27-33 ◽  
Author(s):  
David C. Kossor ◽  
Howard D. Colby
Keyword(s):  
Guinea Pig ◽  
Adrenal Cortex ◽  
Dose Dependent

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

Hepatic uptake of intact glutathione S-conjugate, inhibition by organic anions, and sinusoidal catabolism

1993 ◽  
Vol 265 (3) ◽  
pp. G547-G554
Author(s):  
C. A. Hinchman ◽  
A. T. Truong ◽  
N. Ballatori
Keyword(s):  
Guinea Pig ◽  
Rat Liver ◽  
Marked Decrease ◽  
Hepatic Uptake ◽  
Half Time ◽  
High Concentrations ◽  
Rat Livers ◽  
Dose Dependent ◽  
Uptake And Metabolism ◽  
Guinea Pig Liver

To identify potential mechanisms for hepatic removal of circulating glutathione (GSH) conjugates, uptake and metabolism of S-2,4-dinitrophenylglutathione (DNP-SG) were examined in isolated perfused livers from rat and guinea pig. Guinea pig livers perfused with 5 mumol of DNP-SG in a recirculating system (50 microM initial concn) rapidly cleared the conjugate from the perfusate (half time 3.7 min), whereas clearance was considerably slower in rat liver (half time 35 min). Disappearance of DNP-SG from the perfusate was accompanied by a simultaneous appearance of DNP-SG and its metabolites in bile. Addition of acivicin, an inhibitor of gamma-glutamyltransferase (gamma-GT), to the perfusate resulted in a marked decrease in DNP-SG clearance by guinea pig liver but had no effect in rat liver, suggesting that in the guinea pig this process is largely dependent on sinusoidal gamma-GT activity. However, even in the presence of acivicin, rat and guinea pig livers removed nearly one-half of the administered DNP-SG from the recirculating perfusate over 30 min. High concentrations of DNP-SG were found in bile (up to 3.7 mM), indicating that the liver is capable of transporting the intact conjugate from the circulation. When rat livers were perfused with higher concentrations of DNP-SG (100 and 250 microM), biliary excretion of DNP-SG increased dose dependently, with concentrations in bile reaching 10 mM at the higher dose. This was accompanied by a dose-dependent choleresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory Metabolism During Pregnancy in the Guinea Pig

1957 ◽  
Vol 190 (3) ◽  
pp. 425-428 ◽  
Author(s):  
Richard M. Hoar ◽  
William C. Young
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Guinea Pig ◽  
Metabolic Rate ◽  
Adrenal Cortex ◽  
Guinea Pigs ◽  
Sharp Decrease ◽  
Zona Fasciculata ◽  
Respiratory Metabolism ◽  
Morphological Differences

Oxygen consumption and heart rate during pregnancy were measured in untreated, thyroxin-injected and thyroidectomized guinea pigs given I131. From impregnation until parturition, oxygen consumption increased 7.9% in untreated females. The increase continued until 5 days postpartum when a sharp decrease occurred. The increase is not accounted for by growth of the fetal mass. Comparable increases occurred in thyroxin-injected (16.2%) and thyroidectomized (11.9%) females, although the levels throughout were higher and lower, respectively, than in intact females. Heart rate did not increase. On the contrary, statistically significant decreases occurred in the untreated and thyroxin-injected females. Although the mechanism associated with the increased metabolic rate is not known, the possibility of thyroid participation would seem to be excluded. Involvement of the adrenal cortex is suggested by morphological differences in the cells of the zona fasciculata in pregnant and nonpregnant females and by evidence cited from other studies.

Nuclear Progesterone-Binding Protein in the Guinea Pig Adrenal Cortex: Distinction from the Classical Progesterone Receptor

Endocrinology ◽  
1989 ◽  
Vol 124 (5) ◽  
pp. 2200-2207 ◽  
Author(s):  
TAKAYOSHI DEMURA ◽  
WILLIAM J DRISCOLL ◽  
CHARLES A STROTT
Keyword(s):  
Progesterone Receptor ◽  
Guinea Pig ◽  
Adrenal Cortex ◽  
Binding Protein

Glutathione depletion inhibits amylase release in guinea pig pancreatic acini

1983 ◽  
Vol 244 (3) ◽  
pp. G273-G277
Author(s):  
W. F. Stenson ◽  
E. Lobos ◽  
H. J. Wedner
Keyword(s):  
Guinea Pig ◽  
Reduced Glutathione ◽  
Glutathione Depletion ◽  
Amylase Secretion ◽  
Ionophore A23187 ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Stimulus Secretion Coupling ◽  
Dose Dependent ◽  
Higher Doses

Isolated guinea pig pancreatic acini were specifically depleted of glutathione by treatment with 2-cyclohexene-1-one (2-CHX-1). Untreated acini contained 4.3 +/- 0.6 micrograms of glutathione per milligram protein. Incubation with 1 mM 2-CHX-1 for 5 min at 37 degrees C depleted glutathione to 17% of control values; 5 mM 2-CHX-1 depleted glutathione to less than 4% of control values. Incubation with 2-CHX-1 also impaired the ability of the isolated acini to secrete amylase in response to stimulation with carbachol and the ionophore A23187. The depletion of glutathione and the inhibition of amylase secretion by 2-CHX-1 were both dose dependent and time dependent. Incubation of acini with 2 mM 2-CHX-1 for 15 min at 37 degrees C reduced glutathione levels to 6.6% of control and reduced carbachol-stimulated amylase release to 63% of control. Higher doses of 2-CHX-1 or longer incubations resulted in greater depletion of glutathione and greater inhibition of carbachol-induced amylase release. These data indicate that specific depletion of glutathione impairs the ability of isolated acini to secrete amylase in response to physiological and pharmacologic stimuli and suggest that glutathione has a role in stimulus-secretion coupling in the exocrine pancreas.

Neurokinin receptor mediated plasma extravasation in guinea pig and rat airways: comparison of 125I-labelled human fibrinogen and 99mTc-labelIed human serum albumin as markers of leakage

1993 ◽  
Vol 71 (7) ◽  
pp. 506-511 ◽  
Author(s):  
Christine Tousignant ◽  
Chi-Chung Chan ◽  
Donna Young ◽  
Diane Guevremont ◽  
Ian W. Rodger
Keyword(s):  
Human Serum Albumin ◽  
Guinea Pig ◽  
Serum Albumin ◽  
Human Serum ◽  
Plasma Extravasation ◽  
Human Fibrinogen ◽  
Protein Extravasation ◽  
Neurokinin Receptor ◽  
Lower Airways ◽  
Dose Dependent

In the present study we have characterized NK-1 and NK-2 receptor induced microvascular leakage in guinea pig and rat airways, using 125I-labelled human fibrinogen ([125I]FN) versus 99mTc-labelled human serum albumin ([99mTc]HSA) as markers for plasma protein extravasation. Intravenous administration of the selective NK-1 agonist [Sar9, Met(O2)11]SP (1 nmol kg−1) caused a dose-dependent increase of [125I]FN extravasation in guinea pig trachea, main bronchi, secondary bronchi, and intraparenchymal airways. Extravasation of [125I]FN increased by up to 192 (trachea), 284 (main bronchi), 368 (secondary bronchi), and 271% (intraparenchymal bronchi) over control levels in these regions of the airways. Pretreatment of the animals with CP 99,994 and RP 67,580, two NK-1 nonpeptide antagonists, caused a dose-dependent inhibition of [Sar9, Met(O2)11]SP-induced leakage of [125I]FN. [Sar9, Met(O2)11]SP (1 nmol kg−1) did not induce specific leakage of [99mTc]HSA in the intraparenchymal bronchi. Specific NK-2 receptor induced leakage was detected in the lower airways but only when using [125I]FN as a marker. We have also compared the ability of CP 99,994 and RP 67,580 to inhibit [Sar9, Met(O2)11]SP induced extravasation of [125I]FN in rat airways. CP 99,994 was 40–50 (tracheobronchial region) to 75 (lower airways) times more potent in the guinea pig than the rat airways. In contrast, RP 67,580 had higher affinity for rat airways compared with guinea pig airways. The results of this study highlight the superiority of [125I]FN as a sensitive marker of plasma extravasation over [99mTc]HSA. Furthermore, the results strongly suggest that both NK-1 and NK-2 receptors mediate plasma extravasation in the guinea pig lower airways and that NK-1 receptors are different in guinea pig and rat airways.Key words: Leakage, tachykinins, NK-1 and NK-2 receptors, airway, asthma.

Age-related changes in gallbladder contractility and cytoplasmic Ca2+ concentration in the guinea pig

1993 ◽  
Vol 264 (4) ◽  
pp. G624-G629 ◽  
Author(s):  
J. Ishizuka ◽  
M. Murakami ◽  
G. A. Nichols ◽  
C. W. Cooper ◽  
G. H. Greeley ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Contractile Force ◽  
Binding Ability ◽  
Age Related ◽  
Displacement Transducers ◽  
Force Displacement ◽  
Dose Dependent Increase ◽  
Muscle Compliance ◽  
Dose Dependent

Gallbladder (GB) motility diminishes with aging. This study was performed to characterize mechanisms that are involved in changes in GB contractility that occur during aging. Cytoplasmic Ca2+ concentrations ([Ca2+]i) and the contractile force of guinea pig GB muscle strips were simultaneously measured using fura-2 and force-displacement transducers. The binding ability of the Ca2+ channel antagonist and GB muscle compliance were also examined. The COOH-terminal octapeptide of cholecystokinin (CCK-8) evoked a dose-dependent increase in force and [Ca2+]i. Changes of [Ca2+]i and contractile force of muscle strips in response to CCK-8 were significantly greater in young (2 mo old) compared with mature and aged (12 and 24 mo old) guinea pigs (changes in [Ca2+]i, ED50: 46.1 nM at 2 mo, 6.1 microM at 12 mo, and 2.8 mM at 24 mo; changes of contractile force, ED50: 24.8 microM at 2 mo, 2.1 mM at 12 mo, and 357 mM at 24 mo). However, the magnitude of the contraction at each percent change in [Ca2+]i was actually similar in young and aged guinea pigs. In a Ca(2+)-free buffer, the responses of [Ca2+]i and force to CCK-8 in both young and aged GB muscles decreased, but those were still dose and age dependent. Binding ability of the Ca2+ channel antagonist did not differ in the young and aged groups, but the compliance of the GB muscle strip decreased with aging. These results suggest that both a reduced mobilization of intracellular Ca2+ and a decreased muscle compliance are responsible, at least in part, for age-related reduced contraction of guinea pig GB in response to CCK.

Endothelium-dependent and -independent relaxations to adenosine in guinea pig aorta

1990 ◽  
Vol 259 (1) ◽  
pp. H62-H67 ◽  
Author(s):  
J. P. Headrick ◽  
R. M. Berne
Keyword(s):  
Guinea Pig ◽  
Sodium Nitroprusside ◽  
Maximal Response ◽  
Dependent Manner ◽  
Prostaglandin F2 Alpha ◽  
Endothelial Response ◽  
Alpha Response ◽  
Dose Dependent ◽  
Subtype 3 ◽  
Indomethacin Treatment

Effects of endothelial removal and hypoxia on responses to adenosine, 5'-(N-ethylcarboxamido)-adenosine (NECA), 2-chloroadenosine, N6-cyclohexyladenosine (CHA), sodium nitroprusside, and acetylcholine were examined in guinea pig aortic rings. Rings contracted with 2 microM prostaglandin F2 alpha (PGF2 alpha) relaxed in a dose-dependent manner in response to all drugs. The order of potency of adenosine compounds was NECA greater than 2-chloroadenosine greater than adenosine greater than CHA. Endothelial rubbing potentiated the PGF2 alpha response by 11 +/- 3%, eliminated the acetylcholine (ACh) response, but had no effect on nitroprusside and CHA responses. Responses to adenosine, NECA, and 2-chloroadenosine were significantly depressed by rubbing (P less than 0.05). Oxyhemoglobin (5 microM) and metyrapone (0.1 mM) reduced ACh responses in intact rings but had no effect on the adenosine and nitroprusside responses. Indomethacin treatment (10 microM) did not alter ACh, nitroprusside, or adenosine responses in intact rings. Hypoxia (10% O2) potentiated maximal responses to adenosine (+26 +/- 3%) and nitroprusside (+28 +/- 4%) in intact and rubbed rings and reduced the maximal response to ACh in intact rings (-28 +/- 3%). It is concluded that 1) adenosine mediates relaxation in guinea pig aorta by endothelial-dependent and -independent mechanisms, 2) receptors involved in both endothelial-dependent and -independent relaxations are characteristic of the A2 adenosine subtype, 3) the endothelial response appears unrelated to EDRF or prostanoid release, and 4) the adenosine response is significantly potentiated by hypoxia.

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