Nongenomic effect of testosterone on chloride secretion in cultured rat efferent duct epithelia.
(57/653)
Short-circuit current (I(sc)) technique was used to investigate the role of testosterone in the regulation of chloride secretion in cultured rat efferent duct epithelia. Among the steroids tested, only testosterone, and to a lesser extent, 5alpha-dihydrotestosterone (5alpha-DHT), reduced the basal and forskolin-induced I(sc) in cultured rat efferent duct epithelia when added to the apical bathing solution. Indomethacin, a 3alpha-hydroxysteroid dehydrogenase, did not affect the inhibitory effect of 5alpha-DHT. The effect of testosterone occurred within 10-20 s upon application and was dose dependent with apparent IC(50) value of 1 microM. The effect was abolished by removal of Cl(-) but not HCO from the normal Krebs-Henseleit solution, suggesting that testosterone mainly inhibited Cl(-) secretion. The efferent duct was found to be most sensitive to testosterone, while the caput and the cauda epididymidis were only mildly sensitive. Cyproterone acetate, a steroidal antiandrogen, or flutamide, a nonsteroidal antiandrogen, did not block the effect of testosterone on the forskolin-induced I(sc), nor did protein synthesis inhibitors, cycloheximide, or actinomycin D. However, pertussis toxin, a G(i) protein inhibitor, attenuated the inhibition of forskolin-induced I(sc) by testosterone. Testosterone caused a dose-dependent inhibition of forskolin-induced rise in cAMP in efferent duct cells. It is suggested that the rapid effect of testosterone was mediated through a membrane receptor that is negatively coupled to adenylate cyclase via G(i) protein. The role of nongenomic action of testosterone in the regulation of electrolyte and fluid transport in the efferent duct is discussed. (+info)
Correlation of cerebrovascular reserve as measured by acetazolamide-challenged SPECT with angiographic flow patterns and intra- or extracranial arterial stenosis.
(58/653)
BACKGROUND AND PURPOSE: The ability to identify patients at increased risk for stroke from cerebral hemodynamic ischemia may help guide treatment planning. We tested the correlation between regional cerebrovascular reserve (rCVR) on acetazolamide-challenged single-photon emission CT (SPECT) brain scans and intracranial collateral pathways as well as extra- or intracranial (EC-IC) arterial stenosis on cerebral angiography. METHODS: A retrospective analysis of 27 patients who underwent cerebral angiography and acetazolamide-challenged SPECT brain imaging was performed. With cerebral angiography, the anterior, middle, and posterior cerebral artery (ACA, MCA, PCA) territories were evaluated for patterns of flow, including the ipsilateral carotid or basilar arteries, the circle of Willis collaterals, the EC-IC collaterals, and the leptomeningeal collaterals. With acetazolamide-challenged SPECT, the ACA, MCA, and PCA territories were classified as either showing or not showing evidence of decreased rCVR. Statistical significance was determined by the chi(2) test. RESULTS: Patients with decreased rCVR had significantly greater dependence on either the EC-IC or leptomeningeal collaterals (42%) than did patients without decreased rCVR (7%). Similarly, the cerebral hemispheres with decreased rCVR showed a higher prevalence of 70% or greater stenosis or occlusion of the ipsilateral EC-IC arteries in the anterior circulation (74%) than did hemispheres with no evidence of decreased rCVR (16%), and this difference was also statistically significant. CONCLUSION: Acetazolamide-challenged SPECT brain scanning provides additional information regarding rCVR that is not reliably provided by cerebral angiography. (+info)
Factors governing the transepithelial potential difference across the proximal tubule of the rat kidney.
(59/653)
Previous measurements of the transepithelial potential difference (PD) of the proximal tubule have yielded widely conflicting values (range -20 to +3 mV). In a recent study, Kokko has demonstrated that the PD of the in vitro perfused isolated proximal tubule of the rabbit varies in a predictable way from -6 to +3 mV, depending on the concentration of chloride, bicarbonate, glucose, and amino acids in the perfusing solution. The present micropuncture study examines the effect of tubular fluid composition on the PD profile along the proximal tubule of the in vivo rat kidney. Low resistance measuring electrodes with large tips (3-5 microns OD) filled with 3 M KCl, were used to provide stable PD recordings. Experiments were performed to validate the use of these electrodes. Transepithelial PD measurements were made in immediate postglomerular segments identified by injection of dye into Bowman's space of accessible surface glomeruli and in randomly selected more distal segments of the proximal tubule. In the control state, the first loop was found to have a small but consistently negative PD which could be obliterated by an infusion of phloridzin. In contrast, the PD in later segments was consistently positive. Infusion of acetazolamide abolished the positive PD in the later segments. Acetazolamide and glucose infusion resulted in a negative PD which was abolished by the additional infusion of phloridzin. These data provide evidence that glucose reabsorption is electrogenic and can account for the small negative PD normally present in the early proximal tubule. The positive PD in later segments appears to be a passive chloride diffusion potential. This positive potential is discussed as an important electrochemical driving force for significant passive reabsorption of sodium in the proximal tubule. (+info)
Abolition of pentagastrin-stimulated alkaline tide using the carbonic anhydrase inhibitor acetazolamide.
(60/653)
BACKGROUND: Alkaline tide is the transient increase in blood and urine pH following stimulation of gastric acid secretion. It is attributed to HCO3- release from parietal cells in parallel with H+ secretion. The enzyme carbonic anhydrase is thought to be responsible for HCO3- production from CO2 and OH- in the parietal cell. OBJECTIVE: To examine the effect of pretreatment with the carbonic anhydrase inhibitor, acetazolamide, on the alkaline tide phenomenon. METHODS: Ten patients with dyspepsia and demonstrable alkaline tide were tested on three separate days. The pH and base excess were determined in arterialized venous blood before and 45 minutes after an intramuscular injection of pentagastrin. The pH of the urine was measured before and 120 min after pentagastrin injection. Measurements were performed after pentagastrin alone on day 1, following pretreatment with acetazolamide 60 min before pentagastrin on day 2, and after the administration of acetazolamide alone on day 3. RESULTS: Following the administration of pentagastrin alone, the blood base excess increased by 1.61 +/- 0.2 mEq/L (mean +/- standard deviation) and the calculated alkaline tide at 45 min was 33.99 +/- 4.49 mEq. On day 2 with prior administration of acetazolamide, base excess decreased by 0.21 +/- 0.39 mEq/L, and the calculated alkaline tide was -3.28 +/- 7.57 mEq, which was significantly lower than on day 1 (P = 0.0001). On day 3, following acetazolamide alone, the base excess values decreased by 0.53 +/- 0.2 mEq/L and the alkaline tide was -10.05 +/- 3.33 mEq; there was no significant difference compared with day 2 (P = 0.44). CONCLUSION: Pretreatment with acetazolamide abolished the alkaline tide induced by pentagastrin. This finding supports the view that carbonic anhydrase has a major role in the alkaline tide phenomenon. (+info)
Model of ionic transport for bovine ciliary epithelium: effects of acetazolamide and HCO.
(61/653)
The possible existence of transepithelial bicarbonate transport across the isolated bovine ciliary body was investigated by employing a chamber that allows for the measurement of unidirectional, radiolabeled fluxes of CO2 + HCO. No net flux of HCO was detected. However, acetazolamide (0.1 mM) reduced the simultaneously measured short-circuit current (I(sc)). In other experiments in which (36)Cl- was used, a net Cl- flux of 1.12 microeq. h(-1). cm(-2) (30 microA/cm(2)) in the blood-to-aqueous direction was detected. Acetazolamide, as well as removal of HCO from the aqueous bathing solution, inhibited the net Cl- flux and I(sc). Because such removal should increase HCO diffusion toward the aqueous compartment and increase the I(sc), this paradoxical effect could result from cell acidification and partial closure of Cl- channels. The acetazolamide effect on Cl- fluxes can be explained by a reduction of cellular H+ and HCO (generated from metabolic CO2 production), which exchange with Na+ and Cl- via Na+/H+ and Cl-/HCO exchangers, contributing to the net Cl- transport. The fact that the net Cl- flux is about three times larger than the I(sc) is explained with a vectorial model in which there is a secretion of Na+ and K+ into the aqueous humor that partially subtracts from the net Cl- flux. These transport characteristics of the bovine ciliary epithelium suggest how acetazolamide reduces intraocular pressure in the absence of HCO transport as a driving force for fluid secretion. (+info)
Pharmacological enhancement of synaptic efficacy, spatial learning, and memory through carbonic anhydrase activation in rats.
(62/653)
CA1 pyramidal cells were recorded in rat hippocampal slices. In the presence of carbonic anhydrase activators, comicrostimulation of cholinergic inputs from stratum oriens and gamma-aminobutyric acid (GABA)ergic inputs from stratum pyramidale at low intensities switched the hyperpolarizing GABA-mediated inhibitory postsynaptic potentials to depolarizing responses. In the absence of the activators, however, the same stimuli were insufficient to trigger the synaptic switch. This synaptic switch changed the function of the GABAergic synapses from excitation filter to amplifier and was prevented by carbonic anhydrase inhibitors, indicating a dependence on HCO. Intralateral ventricular administration of these same carbonic anhydrase activators caused the rats to exhibit superior learning of the Morris water maze task, suggesting that the GABAergic synaptic switch is critical for gating the synaptic plasticity that underlies spatial memory formation. Increased carbonic anhydrase activity might, therefore, also enhance perception, processing, and storing of temporally associated relevant signals and represents an important therapeutic target in learning and memory pharmacology. (+info)
Miotics in closed-angle glaucoma.
(63/653)
The use of intravenous Diamox with variable doses of Pilocarpine was investigated in the treatment of primary closed-angle glaucoma. It was concluded that one drop of Pilocarpine 3 to 4 hrs after intravenous Diamox is the only parasympathomimetic drug necessary to terminated an acute attack. (+info)
The effect of sodium salicylate on bile secretion in the dog.
(64/653)
1. The I.V. injection of sodium salicylate (100 mg/kg) in the dog caused a rapid and maintained choleresis of the order of 300-600 percent of control levels. 2. The total amount of salicylate excreted in bile was only 1-2 percent of that injected. 3. The secretion of bile salt into bile was not increased by salicylate. 4. The choleresis caused by salicylate was associated iwth a decrease in the concentrations of sodium and of bile salt in bile, and with an increase in the concentration of chloride; the biliary concentration of bicarbonate was either temporarily increased or unchanged. 5. The choleresis could not be inhibited by the intra-portal injection of of ouabain (0-1 mg/kg). 6. The secretion of bromsulphthalein into bile was not potentiated by the choleresis. 7. The choleretic efficiency of sodium taurocholate was not increased in the presence of salicylate. 8. The injection of acetazolamide (20 mg/kg) in the presence of a salicylate choleresis, caused an increase in the osmolaity of bile and an increase in biliary sodium concentration, such that the composition of bile more nearly approached that of plasma. 9. The possible mechanisms underlying the choleretic effect of sodium salicylate are discussed. (+info)