The balance and cross-talk between natruretic and antinatruretic hormone receptors plays a critical role in the regulation of renal Na ؉ homeostasis, which is a major determinant of blood pressure. Dopamine and angiotensin II have antagonistic effects on renal Na ؉ and water excretion, which involves regulation of the Na ؉ ,K ؉ -ATPase activity. Herein we demonstrate that angiotensin II (Ang II) stimulation of AT1 receptors in proximal tubule cells induces the recruitment of Na ؉ ,K ؉ -ATPase molecules to the plasmalemma, in a process mediated by protein kinase C␤ and interaction of the Na ؉ ,K ؉ -ATPase with adaptor protein 1. Ang II stimulation led to phosphorylation of the ␣ subunit Ser-11 and Ser-18 residues, and substitution of these amino acids with alanine residues completely abolished the Ang II-induced stimulation of Na ؉ ,K ؉ -ATPase-mediated Rb ؉ transport. Thus, for Ang II-dependent stimulation of Na ؉ ,K ؉ -ATPase activity, phosphorylation of these serine residues is essential and may constitute a triggering signal for recruitment of Na ؉ ,K ؉ -ATPase molecules to the plasma membrane. When cells were treated simultaneously with saturating concentrations of dopamine and Ang II, either activation or inhibition of the Na ؉ ,K ؉ -ATPase activity was produced dependent on the intracellular Na ؉ concentration, which was varied in a very narrow physiological range (9 -19 mM). A small increase in intracellular Na ؉ concentrations induces the recruitment of D1 receptors to the plasma membrane and a reduction in plasma membrane AT1 receptors. Thus, one or more proteins may act as an intracellular Na ؉ concentration sensor and play a major regulatory role on the effect of hormones that regulate proximal tubule Na ؉ reabsorption.

1. Activity patterns across and within the laminae of the olfactory bulb were analyzed by imaging voltage-sensitive dye responses during odorant stimulation of all or part of the ventral olfactory mucosa. 2. The time course of the signals was generally characterized by a brief, small hyperpolarization, followed by a period of depolarization, and then a longer-lasting hyperpolarization similar to that seen with electric stimulation but with longer durations. 3. The activity was distributed nonhomogeneously across the bulbar laminae in the form of spatially segregated clusters having bandlike appearances. Clusters were observed with three monomolecular odorants, amyl acetate, ethyl-n-butyrate, and limonene, and with the complex odor of meal worms. Although response patterns to different odorants overlapped, they also showed differences in overall distribution. 4. Delivery of high odorant concentrations increased the size of the activated areas and accentuated the degree of response pattern overlap among different odorants. The general properties of the response patterns generated by each odorant were, however, similar at different odorant concentrations and in each of the animals tested. 5. The spatial and temporal distributions of the bulbar responses were somewhat similar regardless of whether the odorants were applied to local epithelial regions via punctate stimulation or to the entire mucosa. Certain regions did, however, have lower thresholds than others for eliciting bulbar activity in response to particular odorants. 6. Odorants applied to regions of the epithelium outside the areas of maximum sensitivity elicited odorant-related activity patterns with depolarizing and hyperpolarizing components similar to those seen with overall stimulation, but only if higher concentrations were used. Activation of distributed odorant sensitivities presumably gave rise to these patterns. 7. These data suggest that subsets of odorant receptor types are found in different areas of the olfactory epithelium, and demonstrate that there is widespread distribution across the epithelium of receptors sensitive to particular odorants. On the basis of the structure of these epithelial fields and the bulb response patterns that they relate to, these findings also provide evidence for complex spatial relationships between the olfactory epithelium and bulb. 8. The findings from this study suggest that representation of odor information in the salamander olfactory bulb does not occur by activation of a few selective bulbar regions, each related to a different odorant species. Instead, large regions of bulbar circuitry are involved in which molecular epitopes may be the unit of representation. Incorporation of new data presented here into a hypothesis of odor coding is discussed.

Na+ reabsorption is regulated in proximal tubules by hormones that stimulate protein kinase C (PKC). To determine whether stimulation of PKC causes a reduction in intracellular Na+ concentration ([Na+]i) that might link Na+ pump activation to increased Na+ reabsorption, [Na+]i was measured in kidney cells loaded with the Na+-sensitive fluorescent indicator SBFI. Rapid digital imaging fluorescence microscopy determinations were performed in epithelial kidney cells transfected with the rodent Na+ pump alpha1 cDNA. In 42 determinations, the basal [Na+]i was 19.7 +/- 2.4 mM. Stimulation of PKC reduced the [Na+]i to 5.6 +/- 0.6 mM in approximately 10 sec. This drastic change in [Na+]i requires a transient 74-120-fold increase in Na+ pump activity. After the new steady state [Na+]i is reached, the Na+ pump is 58% activated. The entry of Na+ into the cells is not affected by stimulation of PKC; therefore, the reduction in [Na+]i is exclusively dependent on activation of the Na+ pump. Accordingly, PKC stimulation does not affect the [Na+]i of cells expressing a mutant Na+ pump that is not stimulated by PKC. The decrease in [Na+]i observed in cells transfected with the rodent Na+ pump alpha1 cDNA is large and sufficiently fast that it is expected to stimulate rapidly passive Na+-influx into the cells, thereby accounting for the observed PKC-induced stimulation of Na+ reabsorption.

ACE DD genotype may be considered a risk factor for the development of common carotid intima-media thickening in our study population.