Inhibition Of HCO3 Research Articles

Effects of Catecholamines on Gas Exchange and Ventilation in Rainbow Trout (Salmo Gairdneri)

ABSTRACT A transient inhibitory effect of catecholamines on relative CO2 excretion, mediated by an inhibition of HCO3− dehydration through the red blood cell (RBC), has been proposed to cause the increase in routinely observed after strenuous exercise in fish (‘CO2 retention hypothesis’, Wood and Perry, 1985). To evaluate this idea, trout fitted with arterial cannulae, oral membranes and opercular catheters were placed in ventilation chambers. , RBC intracellular pH (pHi) and other blood acid-base parameters were monitored from the arterial cannulae. The ventilation chamber system allowed continuous, almost instantaneous, measurements of water ΔO2 and ΔCO2 across the gills, and therefore of respiratory exchange ratio (RE), as well as Δammonia, mean expired pH and ventilation volume . Physiological doses of adrenaline and noradrenaline (3.2 nmol kg−1), designed to duplicate typical post-exercise concentrations, together with appropriate saline controls, were injected into resting fish. Adrenaline caused an immediate hypoventilation, while the response to noradrenaline was biphasic: hyperventilation followed by hypoventilation. With both drugs, ΔO2 and ΔCO2 increased, but RE remained constant (adrenaline) or increased (noradrenaline). There was no evidence of a specific inhibition of CO2 excretion, nor was there any increase in ; changes in RBC pHi were small (noradrenaline) or non-existent (adrenaline). These results confirm those of Steffensen el al. (1987) and do not support the CO2 retention hypothesis. However, the RBCs of resting trout may be relatively insensitive to catecholamines at normal arterial blood pH (pHa).

Effects of External Mg2+ and Ph on the Photosynthetic Activities and Stromal pH of Intact Chloroplasts Isolated From C4 Plants

Exogenous Mg2+ inhibited PGA- and OAA-dependent photosynthetic O2 evolution by isolated mesophyll chloroplasts from Zea mays and also HCO3--dependent O2 evolution by chloroplasts from Panicum miliaceum bundle sheath cells. Inhibition of 50-75% was observed with 3-5 mM Mg2+; this varied to some extent with pH but was not reversed by K+ . Inhibition of HCO3-- and PGA-dependent O2 evolution by the divalent cation ionophore A23187 was reversed by adding Mg2+ . Notably, HCO3-- dependent O2 evolution by isolated bundle sheath cells from P. miliaceum was not inhibited by [Mg2+] up to 20 mM. Addition of Mg2+ in the light decreased the stromal pH of mesophyll chloroplasts by less than 0.2 units but reduced apparent stromal volume by as much as 25%. At least for bundle sheath chloroplasts, stromal pH varied with external pH over the range from 7 to 8 but remained about 0.3 units higher throughout this range. Oxygen evolution by isolated mesophyll chloroplasts, and bundle sheath cells and chloroplasts, was relatively insensitive to external pH in the range from 7 to 8. The results are considered in terms of likely mechanisms for the effects of exogenous Mg2+ and pH on photosynthesis by isolated chloroplasts and the physiological significance of Mg2+ effects.

Role of bicarbonate in biliary excretion of diisothiocyanostilbene disulfonate.

Hepatic transport of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) was studied in isolated perfused rat livers and in isolated rat hepatocytes to determine if DIDS-induced decrease in biliary HCO3- excretion is due to a DIDS-HCO3- exchange and/or due to inhibition of Cl(-)-HCO3- exchange. In isolated perfused rat livers, DIDS reversibly decreased biliary HCO3- concentration and excretion. The changes in biliary HCO3- concentration were inversely related to biliary DIDS concentration. DIDS was concentrated in bile, indicating active hepatic transport. Replacement of perfusate HCO3- with equimolar dimethyloxazolidinedione (DMO) or tricine decreased biliary excretion, but not hepatic uptake, of DIDS. Biliary excretion of DIDS was also associated with a decrease in bile pH, and this decrease in pH was greater in the presence of HCO3-. HCO3-, but not DMO or tricine, stimulated DIDS efflux from preloaded hepatocytes. DIDS efflux was also temperature dependent and increased with increasing extracellular pH. Collectively, these results are consistent with the presence of a DIDS-HCO3- (OH-) exchange mechanism at the canalicular membrane. HCO3(-)-dependent Cl- uptake in hepatocytes was competitively inhibited by DIDS (Ki = 0.24 mM), confirming the presence of DIDS-inhibitable Cl(-)-HCO3- exchange. However, the ability of DIDS to decrease biliary HCO3- excretion persisted when perfusate Cl- was replaced by isethionate. Moreover, biliary HCO3- concentration returned to base line despite the presence of 2-6 mM DIDS in bile. Thus it seems unlikely that the inhibition of Cl(-)-HCO3- exchange by DIDS is a major mechanism of inhibition of HCO3- excretion. We, therefore, conclude that a DIDS-HCO3- (OH-) exchange at the canalicular membrane is the most likely explanation for the observed decrease in biliary HCO3- excretion.

Carbonic anhydrase: General perspective and advances in glaucoma research

AbstractThe chemistry and physiology of carbonic anhydrase are reviewed in relation to pharmacological progress in the development of sulfonamide inhibitors. The major organ systems are briefly dicussed. From the medical point of view, the major thrust is now for the treatment of glaucoma. The physiology of aqueous humor formation with respect to ion transport is discussed, and it is shown that a key event is the catalytic formation of HCO3− from CO2 and OH−. The newly formed HCO3− is linked to NA+ and fluid movement to produce aqueous humor. Inhibition of HCO3− sunthesis sulfonamides reduces aqueous formation and lowers pressure in normals and in glucoma.Four sulfonamides have been used sytemically, the chief being acetazolamide. None of these works topically; they do not reach the ciliary process in adequate concetrations. New programs have begun, searching for sulfonamides of different properties that cross the cornea in effective concetrations to inhibit carbonic anhydrase in the ciliary porcess. The key to the problems seems to be to search for a balance between water and lipid solubility, maintaining high activity against the enzyme. This has been achieved, and new structures described from this and other laboratories lower pressure in the rabbit nearly as well as systemic sulfonamides.Corneal permeabilities to test compounds (in vitro) in rabbit and man are similar, but accession to the auqeous (in vivo) is less in man. This may make the goal difficult, and the reasons for this difference are being explored.

Photosynthetic Carbon Sources of Stream Macrophytes

Rates of photosynthesis of four submerged stream macrophytes were examined under varying pH and composition of inorganic carbon species. Callitriche stagnatis and Sparganium simplex used only CO2 for photosynthesis. Potamogeton crispus and P. pectinatus used HCO3 in addition to CO2, but with much lower efficiency. The photosynthetic rates at air equilibrium and a total inorganic carbon concentration of 5.0 mM were 2–3 times lower than maximum rates at CO2 saturation for the HCO3 users and 10–14 times lower for the CO2 users. The CO2 compensation point of entire plants of Callitriche (2.5 μM) and Sparganium (6.0μM) was well below the equilibrium concentration (15 μM). and the low saturation points (250–500 μM) also pointed to efficient use of CO2. Callitriche and Sparganium compete successfully with HCO3− users in hardwater streams, which have a higher exchange and generation capacity of CO2 than stagnant and more soft waters. Rates of photosynthesis of Potamogeton crispus and P. pectinatus decreased at high pH. Depending on the two alternative hypotheses for HCO3use, this decline can be explained by CO3−− inhibition of HCO3− uptake or by increasing capacity to buffer H+efflux from the plant. Habitats subject to high pH, e. g. small ponds with dense vegetation, may have a strong selection for efficient mechanisms of HCO3 use.

Stimulus-secretion coupling in beta-cells: modulation by pH.

We have examined the influence of changes in pH on the oscillatory pattern of electrical activity (EA) in the beta-cell by altering medium pH (pHo) and using permeable weak buffers to alter intracellular pH (pHi). A decrease in pH in the presence of glucose elicited depolarization to the active phase and constant spike activity, whereas an increase in pH elicited a decrease in spike activity or silent hyperpolarization. On inhibition of HCO3:Cl antiport by addition of DIDS (4,4'-diisothiocyano-2,2'-stilbene disulfonic acid), probenecid, or withdrawal of medium HCO-3, there was an increase in the duration of the active phase. A similar result was obtained on the inhibition of Na:H antiport by the addition of amiloride or the reduction of medium [Na+]. The influence of H+ and glucose has been proposed to decrease K+ permeability (PK). However, the influence of pH on 86Rb+ efflux was most effective at subthreshold or 4.2 mM glucose; only a moderate decrease in PK occurred at 8.3 mM glucose, and no effect was obtained at 16.7 mM glucose. Alteration of pHi, and not pHo, induces similar effects on glucose-induced electrical and secretory events. There is a clear dissociation between the influence of inhibitors of the Na:H and HCO3:Cl antiporters on the electrical and secretory events. DIDS and amiloride increased glucose-induced EA, but markedly inhibited the secretory response to glucose. It is evident that pH modulates the electrical events and cationic fluxes and ultimately influences the transduction of information to the mechanisms controlling the secretory process in the beta-cell.