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R M Edwards

Publications and source records attributed to R M Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1986

On the mechanism of fasting-associated elevations in hypothalamic cyclo(His-Pro) content.

Potential mechanism(s) underlying the fasting-associated rise in hypothalamic cyclo(His-Pro) content was explored by examining the effects of 24-hour fasting on: (i) cyclo(His-Pro) synthesis from TRH, (ii) cyclo(His-Pro) metabolism, and (iii) cyclo (His-Pro) secretion by hypothalamic tissue in vitro. The data presented here show that none of these three variables were altered due to fasting. Two additional potential changes that could cause cyclo(His-Pro) elevations during fasting are suggested. These include an in vivo decrease in hypothalamic cyclo(His-Pro) secretion that may not be apparent in vitro, and/or an increase in the synthesis of cyclo(His-Pro) from a precursor(s) other than TRH.

Aminopeptidases↗
PubMed1986

Dependence of proximal tubule p-aminohippurate secretion on serum proteins and metabolic substrates.

Renal proximal tubules secrete p-aminohippurate (PAH) and other endogenous anionic metabolites into the urine. The extent to which organic anion excretion is regulated is unknown, but recent studies indicate that peritubular serum proteins may have a role. We determined the relative effects of serum proteins and metabolic substrates (citrate, lactate, and alanine) on net PAH secretion in isolated perfused rabbit S2 proximal tubules. Net PAH secretion was calculated from the bath-to-lumen flux of [3H]PAH and the isotope specific activity. We corrected the flux for the important difference in PAH binding between rabbit serum proteins and bovine serum albumin (BSA); rabbit serum proteins (5.7 g/dl) and BSA (6 g/dl) bound 10 microM PAH 21 and 37%, respectively. BSA had no effect, but rabbit serum proteins reversibly inhibited PAH secretion in the presence of metabolic substrates in the bath (40.8%), the perfusate (42.6%), and both media (31.5%). In the absence of metabolic substrates, rabbit serum proteins decreased PAH secretion by only 16.8%. PAH secretion was inhibited by 1 g/dl rabbit serum proteins as effectively as 5.7 g/dl (30.3 and 31.5%, respectively), indicating that PAH transport is very sensitive to inhibition by rabbit serum proteins. In the absence of rabbit serum proteins, metabolic substrates in the bath had no effect on PAH secretion. We conclude that rabbit serum proteins inhibit basolateral membrane transport of PAH in proximal tubules. Inhibition by serum proteins is enhanced by bath or lumen citrate, alanine, and lactate, suggesting that peritubular plasma proteins and tubule cell metabolism may interact to modulate proximal tubule organic anion secretion and urinary excretion.

Aminohippuric Acids↗
PubMed1985

Biochemical transmethylation of lipids and neuropeptidergic stimulation of pituitary hormone secretion.

S-adenosyl-L-methionine-dependent methylation of membrane phosphatidylethanolamine to phosphatidylcholine has been shown to exist in a number of tissues including pituitary gland and to play important roles in receptor-mediated functions. The possible role of this phospholipid methylation reaction in pituitary hormone secretion has been studied. To this end, the ability of thyrotropin-releasing hormone (TRH) to release thyrotropin (TSH) and prolactin and the ability of luteinizing hormone-releasing hormone (LH-RH) to release luteinizing hormone (LH) were evaluated after inhibition of pituitary phospholipid methylation. Both TRH and LH-RH stimulated the release of their corresponding pituitary hormone in a dose-dependent manner and this stimulatory effect was inhibited in the presence of phospholipid methylation inhibitors. Non-specific stimulation of TSH release by 55 mM KCl or 0.1 mM veratridine, however, was not affected by the methylation inhibitors. The data suggest that phospholipid methylation may participate in receptor-mediated release of pituitary hormones.

Animals↗
PubMed1985

Response of isolated renal arterioles to acetylcholine, dopamine, and bradykinin.

The effect of acetylcholine (ACh), dopamine (DA), and bradykinin (BK) on vascular tone was examined in interlobular arteries and superficial afferent and efferent arterioles isolated from rabbit kidney. A single microvessel was dissected and cannulated, and lumen diameter was measured at a fixed intraluminal pressure. ACh caused a dose-dependent relaxation of norepinephrine-induced tone in all three vessel types. Significant relaxation (10-20%) was observed with 10(-8) M ACh and higher concentrations caused complete relaxation. In afferent and efferent arterioles DA caused a dose-dependent relaxation that was indistinguishable from the one caused by ACh. However, DA was much less effective on interlobular arteries. Significant relaxation was not observed until 10(-5) M DA, and 10(-4) M caused only a 30-40% relaxation. In afferent arterioles atropine blocked the effect of ACh, and metoclopramide selectively inhibited DA-induced relaxation. BK (10(-9) to 10(-5) M) caused a dose-dependent relaxation of norepinephrine-induced tone only in efferent arterioles. BK, either in the bath or lumen, had no effect on the preglomerular microvessels. ACh and DA also caused relaxation of afferent arterioles with spontaneous tone while all three vasodilators relaxed efferent arterioles with spontaneous tone. The results demonstrate segmental heterogeneity for these vasodilators in the rabbit renal microvasculature, with ACh causing relaxation in all three vessel types, DA acting primarily on the glomerular arterioles, and BK affecting only the efferent arteriole.

Acetylcholine↗
PubMed1985

Effects of prostaglandins on vasoconstrictor action in isolated renal arterioles.

The effects of arachidonic acid, prostaglandins (PG) I2, E2, D2, and F2 alpha on norepinephrine- (NE) and angiotensin II- (ANG II) induced tone were examined in interlobular arteries and afferent and efferent arterioles isolated from rabbit kidney. Arachidonic acid at 10(-5) M produced a rapid relaxation of NE-induced tone in all three vessel types. The vasodilatory effect of arachidonic acid but not acetylcholine was blocked by meclofenamate. In interlobular arteries, PGE2, and PGI2 caused a dose-dependent relaxation of NE-induced tone with a concentration causing the half-maximal response (ED50) of 1.2 and 4.6 X 10(-8) M, respectively. PGD2 caused a small but significant relaxation at 10(-7) M and above, whereas PGF2 alpha was inactive. In afferent arterioles contracted with NE, PGE2 and PGI2 caused identical dose-dependent relaxations. Significant effects were observed at concentrations between 10(-11) and 10(-10) M with ED50 values of 1.7 X 10(-8) M for PGE2 and 8.7 X 10(-9) M for PGI2. PGD2 had significant effects only at 10(-5) M, whereas PGF2 alpha was without effect. In contrast to the preglomerular vessels, efferent arterioles responded only to PGI2 (ED50, 9.7 X 10(-9) M), and the other arachidonic acid metabolites had no effect on lumen diameter. PGI2 antagonized the vasoconstrictive effects of both NE and ANG II in this vessel segment. The results demonstrate that of the prostanoids tested only PGE2 and PGI2 were effective in antagonizing vasoconstrictor stimuli in isolated renal microvessels. Furthermore, the rabbit renal microvasculature displays segmental heterogeneity for the vasodilatory PGs in that PGI2 affected both pre- and postglomerular arterioles, whereas PGE2 was effective only on the preglomerular microvessels.

Angiotensin II↗
PubMed1984

Thyrotropin-releasing hormone (TRH): apparent receptor binding in rat spinal cord.

Thyrotropin-releasing hormone (TRH) is unevenly distributed throughout the rat central nervous system including spinal cord, where exogenous TRH elicits profound pharmacological effects. [Pro-3H]TRH binds to 30,000 g pellet fraction from the spinal cord saturably, reversibly, and with high affinity (apparent Kd = 24-25 nM). This binding is displaced by TRH and related biologically active, but not inactive, peptides. TRH binding is evenly distributed throughout the rat spinal cord. Characteristics of this binding suggest an association with a physiologically relevant TRH receptor.

Animals↗
PubMed1984

Downregulation of adrenocortical cyclo (His-Pro)-binding sites by cyclo (His-Pro) administration to neonatal but not adult rats.

The specific binding of [3H-Pro]cyclo (His-Pro) to a 27,000 g pellet fraction from rat adrenal gland was studied. Binding sites were exclusively localized in the cortical region of the adrenal gland and exhibited a binding affinity (Kd) of 1.79 +/- 0.21 microM and maximal binding capacity (Bmax) of 123.4 +/- 10.2 pmol/mg protein. In vivo administration of cyclo (His-Pro) to neonatal rats led to the downregulation of cyclo (His-Pro)-binding sites with a decrease in Bmax but not Kd. Such changes were not observed after similar treatments of adult rats. These data suggest a receptor-like characteristic of cyclo (His-Pro) binding sites.

Adrenal Cortex↗
PubMed1984

Characterization and subcellular distribution of specific thyrotropin-releasing hormone binding sites in rat cerebellum.

The specific binding of thyrotropin-releasing hormone (TRH) by 30,000 g pellet fraction was ubiquitously distributed throughout various rat brain regions including cerebellum. Although the cerebellum had the lowest apparent density of specific TRH binding sites found in any of the brain regions studied, it represented a single class of high affinity receptor (KD = 37.73 +/- 4.88 nM, Bmax = 156.0 +/- 5.7 fmol/mg protein, n = 4). Furthermore, the cerebellar synaptic plasma membrane fractions were richly endowed with TRH-binding, two other membrane fractions (light-synaptic plasma membrane and microsomal) exhibited high TRH-binding whereas nuclear, mitochondrial or myelin fractions were devoid of significant binding activity. These data show for the first time the existence of specific TRH-binding in cerebellum, and thus suggest that TRH may modulate cerebellar synaptic functions by acting through a specific high affinity-receptor.

Animals↗
PubMed1984

Regulation of phosphatidylcholine biosynthesis by the methylation pathway in rat pituitary gland.

Rat pituitary extracts catalyze methylation of phosphatidylethanolamine to phosphatidylcholine using S-adenosyl-L-methionine as the methyl donor. In vitro incubation of hemipituitaries with 1 mM 2-methylaminoethanol led to a dose dependent decrease in phosphatidylethanolamine methyltransferase activity as well as the incorporation of the radioactivity from [3H-methyl]-L-methionine into phosphatidyl-choline. The inhibitory effect of 2-methylaminoethanol was selective for phospholipids methylation since protein carboxymethyltransferase and catechol-o-methyltransferase activities were not affected.

Animals↗
PubMed1984

Tryptophanase synthesis in Escherichia coli: the role of indole replacement in supplying tryptophan and the nature of the constitutive mutation tnaR3.

The properties of the tryptophanase constitutive mutation tnaR3 have been investigated. It has previously been reported that mutants carrying tnaR3 grow poorly on medium that selects for constitutive expression of tryptophanase. Our results now show that this poor growth can be explained by the inability of tryptophanase to catalyse the synthesis of L-tryptophan from indole, pyruvate and ammonia at a rate sufficient to allow normal growth. Improved media for the characterization of tryptophanase constitutive mutants are described. The mutation tnaR3 rendered tryptophanase synthesis constitutive (at a different rate that at 37 degrees C is 30% of the fully induced wild-type) and not further inducible. Diploid studies showed that tnaR3 is cis-dominant, but no evidence was found for any effect in trans. In addition to rendering tryptophanase synthesis constitutive, tnaR3 affects the response of tryptophanase synthesis to different growth temperatures.

Escherichia coli↗
PubMed1984

Stimulation of phospholipid methylation and thyroid hormone secretion by thyrotropin.

Synthesis of phosphatidylcholine (PC) by S-adenosylmethionine-dependent methylation of phosphatidylethanolamine has previously been associated with receptor-mediated histamine and pituitary hormone secretion. We investigated stimulation of phospholipid methylation by TSH and its possible role in thyroid hormone secretion. Rat hemithyroids were incubated in Krebs-Henseleit-glucose-BSA buffer and the effect of various treatments on the incorporation of [3H-methyl]L-methionine into PC and T4/T3 secretion was studied. TSH treatment elevated thyroid phosphatidylethanolamine methyltransferase activity, the incorporation of [3H-methyl]methionine into PC, and T4/T3 secretion. The increase in PC synthesis was linear up to 6 h in a dose-dependent fashion (half-maximal stimulation at 2.5 micrograms TSH/ml). Stimulation required protein synthesis, because cycloheximide inhibited the increase in PC synthesis by 77%. Inhibitors of phospholipid methylation (100 microM adenosine + 10 microM L-homocysteine thiolactone + 10 microM erythro-9[2-hydroxy-3-nonyl]adenine) significantly decreased TSH-stimulation of phospholipid methylation but not T3/T4 secretion. In conclusion, stimulation of thyroid phospholipid methylation by TSH is not required for stimulated secretion of thyroid hormones.

Animals↗
PubMed1983

Increased phospholipid methylation in the myocardium of alcoholic rats.

Phospholipid methyltransferase activity is unevenly distributed throughout the contractile and the specialized regions of rat heart. Chronic alcohol treatment stimulated the incorporation of [3H-methyl]-methionine but not [3H-methyl]-choline into phosphatidylcholine by left ventricular slices. The increase in the incorporation of [3H-methyl]-group from [3H-methyl]-methionine into phosphatidylcholine was due to an increase in phospholipid methyltransferase activity.

Alcoholism↗
PubMed1983

Segmental effects of norepinephrine and angiotensin II on isolated renal microvessels.

Interlobular arteries and superficial afferent and efferent arterioles were isolated from rabbit kidney, and the effects of intraluminal pressure, norepinephrine (NE), and angiotensin II (ANG II) on lumen diameter were examined. A single microvessel was dissected and one end was cannulated. The other end of the vessel was occluded and lumen diameter was measured at fixed intraluminal pressures. With step increases in intraluminal pressure over the range of 70-180 mmHg, lumen diameters of the interlobular arteries and afferent arterioles remained constant or decreased by up to 11%. In contrast, lumen diameters of efferent arterioles continued to increase as intraluminal pressure was elevated. In all three vessels NE (10(-9) to 10(-5) M) caused a dose-dependent decrease in lumen diameter. However, only the efferent arteriole responded to ANG II (10(-12) to 10(-8) M). The contractile response of the efferent arteriole to NE or ANG II was localized to the first 50-75 micrometers of the vessel as it emerged from the glomerulus. This finding suggests that smooth muscle cells are located only in this portion of the efferent arteriole. It is concluded that at least part of the autoregulation of renal blood flow can be explained by a myogenic mechanism in preglomerular vessels and that ANG II acts primarily on postglomerular segments of the rabbit renal microcirculation.

Angiotensin II↗
PubMed1983

Evidence for an inhibitor of renal urate and PAH secretion in rabbit blood.

Results of previous studies of urate secretion in isolated perfused S2 segments of the rabbit proximal tubule suggested that a bath of rabbit serum may inhibit urate transport in comparison to a synthetic medium. In the current study we tested for a urate transport inhibitor by determining the steady-state tissue-to-medium ratio (T/M) of [14C]urate in nonperfused S2 segments during incubation in synthetic medium (BSA-Burg) and commercial rabbit serum (RS-PF). With 80-120 microM urate in the bath the T/M ratio was 7.66 +/- 0.53 (n = 29) in BSA-Burg and 5.29 +/- 0.40 (n = 29) in RS-PF. RS-PF decreased the influx of urate into the cells but had no effect on urate efflux. Freshly drawn rabbit serum and plasma also inhibited urate accumulation, and the inhibition was reversible. p-Aminohippurate accumulation was inhibited by RS-PF, but tetraethylammonium bromide uptake was not. RS-PF inhibited transepithelial secretion of urate and PAH, but net fluid absorption was not decreased. The inhibitory material in rabbit serum could not be removed by extensive dialysis (14,000-dalton exclusion), by ultrafiltration (50,000-dalton exclusion), or by charcoal or ethanol extraction. Inhibitory activity was detected in both albumin and globulin fractions of rabbit serum. The relation between bath and intracellular urate concentrations of nonperfused tubules in rabbit serum was sigmoidal, whereas the relation in the BSA-Burg medium was more nearly hyperbolic. We conclude that organic anion transport in rabbit S2 segments is inhibited or suppressed by normal serum and suggest that urate secretion and excretion may be subject to allosteric modification by serum proteins.

Aminohippuric Acids↗
PubMed1983

Inhibition of vasopressin action by vanadate in the cortical collecting tubule.

The effect of vanadate, a potent inhibitor of Na-K-ATPase, on the hydroosmotic response to vasopressin (AVP) and transepithelial voltage (Vt) in cortical collecting tubules was examined. At 37 degrees C, exposure of collecting tubules to bath vanadate (10(-4) M) for 30 min inhibited the increase in hydraulic water permeability (Lp) in response to AVP or 8-bromo-cyclic adenosine monophosphate by 68 and 76%, respectively. When vanadate was present only in the lumen no inhibition of the AVP response was observed. Incubation of tubules with ouabain (10(-5) M) for 30 min inhibited the AVP-induced increase in Lp to the same extent as vanadate. At 25 degrees C, vanadate inhibited the increase in Lp by AVP if added before but not after the hormone. Addition of vanadate to the bath caused a rapid decrease in the lumen-negative Vt that is consistent with Na-K-ATPase inhibition. Luminal vanadate also inhibited Vt but the rate of decrease of Vt was much slower than in the presence of bath vanadate. We conclude that vanadate inhibits the development but not the maintenance of the AVP-induced increase in water permeability in the collecting tubule. Since the effect of ouabain was similar to that of vanadate, the results suggest that inhibition of Na-K-ATPase directly or indirectly interferes with the initiation of the AVP-induced increase in luminal membrane water permeability at a site distal to cAMP formation.

8-Bromo Cyclic Adenosine Monophosphate↗