Renal dopamine-1 receptors in hypertensive inbred rat strains with and without hyperactivity.

Renal dopamine-1 (DA-1) receptors are involved in the regulation of sodium transport in several nephron segments, including the proximal convoluted tubule (PCT). DA-1 receptors in the PCT and cortical collecting duct of normotensive rats are linked to the stimulation of adenylyl cyclase (AC). We have reported a defect in the DA-1 receptor/AC coupling in the PCT of the spontaneously hypertensive rat (SHR) of the Okamoto-Aoki strain. Hyperactivity and hypertension are both expressed in the SHR. To determine if the DA-1 receptor coupling defect is associated with hyperactivity or hypertension, we studied the DA-1 receptor in the PCT of two new inbred rat strains derived from the SHR: the hyperactive WKHA and the hypertensive WKHT rat. Tail-cuff blood pressures taken at 4 weeks indicated that WKHT rats were not hypertensive (86 +/- 3 mm Hg, n = 6), whereas at 12 weeks systolic pressures in both SHR and WKHT rats exceeded 150 mm Hg. Hyperactivity, however, was noted in WKHA rats even at this early age. Basal AC activity was similar in WKHA and WKHT PCT in either age group. In the older rats, the DA-1 agonist fenoldopam (10(-7) mol/L) stimulated AC activity in WKHA (70.6 +/- 16.1 fmol per 3 mm PCT per 20 minutes, n = 3) but not in WKHT PCT (43.3 +/- 5.3 fmol per 3 mm PCT per 20 minutes, n = 4). Gpp(NH)p (10(-5) mol/L), a nonhydrolyzable GTP analogue, stimulated AC activity to a similar extent in WKHA and WKHT PCT.(ABSTRACT TRUNCATED AT 250 WORDS)

A renal dopamine-1 receptor defect in two genetic models of hypertension.

Dopamine (DA), via DA-1 receptors, regulates Na+ transport in the kidneys. Dopamine is synthesized from L-DOPA in the proximal tubule and presumably secreted as an autocrine/paracrine substance to stimulate DA-1 receptors localized on proximal tubular cells. We have previously reported the presence of DA-1 receptors in renal cortical homogenates and on the isolated proximal tubule of the rat and rabbit, consistent with the dopamine autocrine/paracrine model. We have localized DA-1 receptors in the proximal straight tubule of the rabbit, and in the cortical collecting duct of the rabbit and rat, but not in the distal collecting tubule or the cortical thick ascending loop of Henle. The presence of functional DA-1 receptors has been substantiated by the coexistence of DA-1 agonist-stimulated adenylate cyclase activity in the same nephron segments in which DA-r receptors have been found. Increased concentrations of intrarenal dopamine induced by dopamine-beta-hydroxylase inhibition with SKF-102698 caused a down regulation of proximal tubular DA-1 receptors and almost complete ablation of DA-1 agonist stimulated adenylate cyclase activity. Thus, dopamine may play a role in the regulation of DA-1 receptors and their linkage with adenylate cyclase. Since alterations in the renal dopaminergic system have been measured in some forms of experimental hypertension, we studied DA-1 receptors and their coupling to adenylate cyclase in the spontaneously hypertensive rat (SHR).(ABSTRACT TRUNCATED AT 250 WORDS)

Serial magnetic resonance images in a patient with congenital sensory neuropathy with anhidrosis and complications resembling heat stroke.

We report the results of serial computerized tomography (CT) and magnetic resonance imaging (MRI) in a 9-month-old Japanese girl with the rare disorder, congenital sensory neuropathy with anhidrosis (CSNA). She developed a prolonged high fever, anorexia, and weight loss with laboratory findings of hemoconcentration and elevated levels of GOT, LDH and creatine phosphokinase (CK) in May 1995, and was hospitalized. The cerebrospinal fluid (CSF) was normal on admission. Elevation of CSF myelin basic protein on the 16th hospital day suggested a destruction of the myelin sheath. The first MRI performed on the 16th hospital day revealed no marked abnormalities when the patient exhibited a high fever, generalized tonic-clonic convulsions, and impaired consciousness. The patient had a persistent high fever, and developed a second generalized tonic clonic convulsion and became comatose. A second MRI on the 20th hospital day showed a bilateral symmetrical paracentral hypo-intensity of the white matter with occipital hypo-intensity on T2-weighted images. MRI findings were considered to represent the complications of the high fever with a loss of water from the cerebral cortices and deep white matter. MRI and CSF findings indicated the presence of brain damage due to the high fever.

Effects of composition and molecular packing on ionic properties of lipid monolayer having both cationic and anionic head groups.

The effects of composition and molecular packing on the overall ionic property of mixed monolayer involving cationic, anionic and zwitterionic lipids were studied by measuring surface potential change when the concentration of sodium or calcium ions in the aqueous substrate was varied. Those lipids used were N,N-dimethyl-N-n-hexadecyl-n-octadecyl ammonium chloride (DDAC) as cationic lipid, stearic acid (StH) or sodium docosylsulfate (SDocS) as anionic lipid, and 1,2-dipalmitoyl-sn-glycero-3-phosphorylethanolamine (PE) and 1,2-distearoyl-sn-glycero-3-phosphorylcholine (PC) as ampholytic lipids. For the equimolar mixture of StH and DDAC, the reversal of apparent charge is observed when molecular packing exceeds 3.25 X 10(-10) M/cm2. The effect is rendered to the discreteness of cationic and anionic charges in the monolayer. It was also found that the addition of 30% of PC drastically changes the ionic property of PE closer to that of PC.

DA1 dopamine receptors in renal cortical collecting duct.

Renal dopamine DA1 receptors are linked to the regulation of sodium transport. We have previously reported the presence of DA1 receptors in the proximal convoluted tubule (PCT) but not in the distal convoluted tubule. However, the DA1 receptor in the collecting duct, the final determinant of electrolyte transport, has not been studied. DA1 receptors were studied in the microdissected cortical collecting duct (CCD) of rats by autoradiography with use of the selective DA1 radioligand 125I-Sch 23982 and by measurement of adenylate cyclase (AC) activity. Specific binding of 125I-Sch 23982 to CCD was saturable with radioligand concentration. The dissociation constant (Kd) was 0.46 +/- 0.08 nM (n = 5), and the maximum receptor density (Bmax) was 1.41 +/- 0.43 fmol/mg protein (n = 5). The DA1 antagonist Sch 23390 was more effective than the DA1 agonist fenoldopam in competing for specific 125I-Sch 23982 binding. Fenoldopam stimulated AC activity in CCD in a concentration-dependent (10(-9)-10(-6) M) manner. The ability of fenoldopam to stimulate AC activity was similar in CCD and PCT even though DA1 receptor density was 1,000 times greater in the CCD than in the PCT. In additional studies, fenoldopam stimulation of AC activity did not influence vasopressin-stimulated AC activity. We conclude that the DA1 receptor in rat CCD is tightly coupled to AC stimulation and that there is no interaction between DA1 agonist-stimulated and vasopressin-stimulated AC activity in the CCD.

Nephron specificity of dopamine receptor-adenylyl cyclase defect in spontaneous hypertension.

Since DA1 receptors regulate renal tubular sodium transport, it is possible that the reported defect in the coupling between the DA1 dopamine receptor and adenylyl cyclase (AC) in the proximal tubule (PT) is a mechanism for the increased sodium reabsorption in animal models of spontaneous hypertension. Because the distal nephron may participate in the increased sodium retention in the spontaneously hypertensive rat (SHR), we determined whether the defective DA1 receptor-AC coupling described in PT of SHR is also present in the cortical collecting duct (CCD). Radioligand binding studies with the DA1 antagonist 125I-Sch 23982 revealed similar dissociation constants and maximum receptor densities in the CCD from Wistar-Kyoto rats (WKY) and SHR. Fenoldopam, a DA1-selective agonist, stimulated AC activity to a similar extent in CCD from both rat groups. Therefore the defective DA1 receptor-AC coupling in SHR has nephron segment specificity, since it is present in PT but not in CCD. One of the AC-linked dopamine receptors is an intronless D1A cloned from brain, which is also present in PT. Because the coupling defect in the PT may reside in the third cytoplasmic loop (involved in G protein coupling), we compared the sequence of this segment of the cloned D1A receptor using genomic DNA. Because no differences were noted between WKY and SHR, the coupling defect in the PT is not due to a mutation at the third cytoplasmic loop of the D1A receptor.

Secondary-phase-modulation method for open-loop fiber-optic gyroscopes.

A proposed method of secondary phase modulation for open-loop fiber-optic gyroscopes is examined in general terms. To detect the rotation rate of a system through a beat-frequency channel, we employ linearly combined signals with different frequencies for the optical phase modulation. We find that the proper combinations of the modulation frequencies can optimize the sensitivity of gyroscopes. With this method we can employ a high-frequency band for optical phase modulations while keeping relative a lower-frequency band of the detection channel. The theoretically derived result is experimentally confirmed by using a lithium-niobate (LiNbO(3)) optical phase modulator. We also discuss the combination setup with an optical integrated-circuit device and digital signal processing.

Polyacrylamide gel electrophoresis of several proteins in the presence of sodium oligooxyethylene dodecyl ether sulfates or a commercially available analog.

The behavior of water-soluble proteins and a typical membrane protein in polyacrylamide gel electrophoresis was studied in the presence of sodium oligooxyethylene dodecyl ether sulfates with a defined number of oxyethylene units or a commercially available analog with distribution and heterogeneity for the oxyethylene chain length and alkyl group, respectively. It was concluded that most water-soluble proteins do not interact with the anionic surfactants as long as their oxyethylene chain lengths are sufficiently long; the commercially available surfactant binds exceptionally well to beta-lactoglobulin without causing denaturation and subsequent dissociation; such surfactants are expected to solubilize membrane proteins without causing denaturation as judged from the result with Na+,K+-ATPase and are promising as new solubilizing agents for membrane proteins which enable efficient electrophoretic analysis or separation after the solubilization.

Dopamine-1 receptors in the proximal convoluted tubule of Dahl rats: defective coupling to adenylate cyclase.

We have previously reported a defect in the coupling of the renal dopamine-1 receptor (D1) to adenylate cyclase (AC) in the proximal convoluted tubule (PCT) of the spontaneously hypertensive rat (Okamoto-Aoki strain). To determine if this defect is present in another model of hypertension, we microdissected PCTs from Dahl salt-sensitive (DSS) and Dahl salt-resistant (DSR) rats on low- or high-NaCl diet. The ability of two selective D1 agonists, fenoldopam and SND-919-C12, and forskolin to stimulate AC activity in PCT was determined in each of the four groups of rats. Fenoldopam (10(-7) M) and SND-919-C12 (10(-6) M) failed to stimulate AC activity in the PCT of DSS rats whether on a low- or high-NaCl diet. In DSR rats, however, both fenoldopam and SND-919-C12 stimulated AC activity by 289-320% and 220-270%, respectively, whether on a low- or high-NaCl intake. Forskolin (10(-5) M), which directly stimulates AC activity, increased AC activity in all four groups. These studies show that in DSS rats the D1 receptor in the PCT fails to respond to D1 agonists. This defect is not a consequence of the hypertension because it was present in the DSS rats on a low-salt diet and before blood pressure elevation.

Concentrations of human atrial natriuretic peptide in the cord blood and the plasma of the newborn.

Concentrations of human atrial natriuretic peptide (hANP) in the cord blood and the plasma were measured in 25 newborns. The level of hANP in 0 to 1 post-natal days (212.8 +/- 118.1 pg/ml; mean +/- SD) was significantly higher than that in cord blood (69.7 +/- 53.2 pg/ml) (p less than 0.005). There were no significant differences in the levels of hANP at the ages of 0 to 1, 4 and 6 post-natal days. The level of hANP did not show any significant correlation with urinary excretion of Na, urinary Na/Cr or Na/K ratios. Further evaluations should be made in order to clarify the role of hANP during the early post-natal period.

Organ specificity of the dopamine1 receptor/adenylyl cyclase coupling defect in spontaneously hypertensive rats.

The coupling between the dopamine1 (DA1) receptor and the G protein/adenylyl cyclase (AC) enzyme complex is defective in the proximal convoluted tubule (PCT) of 20-wk-old spontaneously hypertensive rats (SHRs). Because this coupling defect could have been due to desensitization secondary to elevated renal dopamine levels in the adult animal, we studied the interaction between DA1 receptors and AC in PCT of rats as early as 3 wk of age, a time when renal dopamine levels are similar in SHRs and their normotensive controls (Wistar-Kyoto rats, WKYs). Maximum receptor density did not change with age and was similar in WKYs and SHRs in all the age groups studied (3, 8, and 20 wk). Basal-, forskolin-, and guanyl nucleotide-stimulated AC activities were also similar in WKYs and SHRs and did not change with age. However, the DA1 agonist-stimulated AC activity was greater in WKYs than in SHRs and increased with age in WKYs but not in SHRs. Moreover, the ability of a nonhydrolyzable analogue of GTP, Gpp(NH)p, to enhance DA1 agonist (SND-919-C12, 1 microM)-stimulated AC activity increased with age in WKY but not in SHRs. To determine if the defect noted in the PCT of SHRs is due to a defective D1A receptor gene, parallel studies were performed in the striatum, since this receptor is expressed predominantly in the latter tissue. In contrast to the results in PCT, radioligand binding and AC studies in striatum revealed no differences between WKYs and SHRs.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydrophilicity of Polar and Apolar Domains of Amphiphiles.

The hydrophilicity of polar and apolar domains of various amphiphiles was systematically estimated for their homologues and analogues by measuring the molar adiabatic compressibility of an aqueous solution at infinite dilution. The homologues of protic alkyl H(CH(2))(n)-, perfluoroalkyl F(CF(2))(n)-, and alkylphenyl H(CH(2))(n)(C(6)H(5))- groups (n=0-10) were chosen to represent apolar hydrophobic domains. The polar hydrophilic domains tested were -SO(4)Na, -SO(3)Na, -COONH(4), -N(CH(3))(3)Br, N(C(m)H(2m+1))(4)Br (m=1-5), and -NH(CH(2))(n)SO(3) (n=3, 4) groups. Also tested were the tetraphenyl ionic compounds (C(6)H(5))(4)MX (M=B/X=Na, M=P/X=Cl, M=As/X=Cl) to study the effect of the ionic sign of the core atom across the tetraphenyl apolar shell, the polyethylene glycols H(OCH(2)CH(2))(m)OH (m=1-4) to study the role of apolar -CH(2)- units in the hydrophilic oxyethylene group, and the zwitterionic dimethylaminoalkylsulfonate (CH(3))(2)NH(CH(2))(n)SO(3) homologues to study the effect of intramolecular salt formation on the hydrophilicity of the zwitterion. The adiabatic compressibility of the solution was calculated from measurement of the sound velocity and density of solutions. The introduction of laboratory automation and the numerical control of the system improved the accuracies and efficiencies of the measurements a great deal. The range of the temperature scan was 0-40 degrees C with an effective accuracy of +/-0.001 degrees C and the concentration was automatically scanned down to far below the cmc of the surfactant. The hydrophilicity of various polar and apolar substances was estimated as the decrease of molar adiabatic compressibility of the aqueous solution with increased concentration of their homologues and analogues. The hydrophobic hydration of nonpolar substances was found to be very small at room temperature and was barely detected above 40 degrees C; however, it became large as the temperature was lowered and attained a maximum at 0 degrees C. The cationic charge of quaternary ammonium N(+)(C(n)H(2n+1))(4) was found to enhance the hydrophobic hydration of methylene groups located at a distance of 4 to 6 Å from the core nitrogen atom, while the terminal negative charge of the anionic surfactant R-SO(4)(-), R-SO(3)(-), or R-COO(-) was found to decrease the hydrophobic hydration of -CH(2)- units within the same range. The hydrophilicity of quaternary ammonium and the tetraphenyl ions should be synergistically given by both hydrophobic and ionic hydrations. The hydrophilicity of the perfluoromethylene unit -CF(2)- was found to have a value comparable to that of the protic methylene unit -CH(2)-. The hydrophobic hydration seems to offer a good measure of the hydrophilicity of apolar substances; however, it does not necessarily represent the "hydrophobicity" of the apolar segment when the "surface activity" of the amphiphile is concerned. Copyright 2000 Academic Press.