Biomedical subjects

R M Edwards

Publications and source records attributed to R M Edwards.

At least 73 records · Page 4Linked to original sources

PubMed1992

Novel mutations in the pheA gene of Escherichia coli K-12 which result in highly feedback inhibition-resistant variants of chorismate mutase/prephenate dehydratase.

The bifunctional enzyme chorismate mutase/prephenate dehydratase (EC 5.4.99.5/4.2.1.51), which is encoded by the pheA gene of Escherichia coli K-12, is subject to strong feedback inhibition by L-phenylalanine. Inhibition of the prephenate dehydratase activity is almost complete at concentrations of L-phenylalanine greater than 1 mM. The pheA gene was cloned, and the promoter region was modified to enable constitutive expression of the gene on plasmid pJN302. As a preliminary to sequence analysis, a small DNA insertion at codon 338 of the pheA gene unexpectedly resulted in a partial loss of prephenate dehydratase feedback inhibition. Four other mutations in the pheA gene were identified following nitrous acid treatment of pJN302 and selection of E. coli transformants that were resistant to the toxic phenylalanine analog beta-2-thienylalanine. Each of the four mutations was located within codons 304 to 310 of the pheA gene and generated either a substitution or an in-frame deletion. The mutations led to activation of both enzymatic activities at low phenylalanine concentrations, and three of the resulting enzyme variants displayed almost complete resistance to feedback inhibition of prephenate dehydratase by phenylalanine concentrations up to 200 mM. In all four cases the mutations mapped in a region of the enzyme that has not been implicated previously in feedback inhibition sensitivity of the enzyme.

Amino Acid Sequence↗

PubMed1992

Activation of endothelin ETB receptors increases glomerular cGMP via an L-arginine-dependent pathway.

The effects of endothelins (ET) on guanosine 3',5'-cyclic monophosphate (cGMP) levels in intact rat glomeruli were examined. ET-3 produced a rapid approximately fivefold increase in cGMP levels with the maximum effect occurring at 1 min. The ET-3-induced increase in cGMP accumulation occurred in the absence and presence of 3-isobutyl-1-methylxanthine. ET-1, ET-2, ET-3, and the structurally related toxin, sarafotoxin S6c, all increased glomerular cGMP levels in a concentration-dependent manner and with similar potencies (EC50 approximately 15-30 nM). The L-arginine analogue, N omega-nitro-L-arginine (L-NNA), reduced basal levels of cGMP and also totally inhibited ET-induced increases in cGMP as did methylene blue, an inhibitor of soluble guanylate cyclase. The effect of L-NNA was attenuated by L-arginine but not by D-arginine. The stimulation of cGMP accumulation by ET-3 was dependent on extracellular Ca2+ and was additive to atriopeptin III but not to acetylcholine. The ETA-selective antagonist, BQ 123, had no effect on ET-3-induced formation of cGMP. Glomerular membranes displayed high-affinity (Kd = 130-150 pM) and high-density (approximately 2.0 pmol/mg) binding sites for 125I-ET-1 and 125I-ET-3. ET-1, ET-3, and sarafotoxin S6c displaced 125I-ET-1 binding to glomerular membranes with similar affinities. BQ 123 had no effect on 125I-ET-1 binding. We conclude that ET increases cGMP levels in glomeruli by stimulating the formation of a nitric oxide-like factor that activates soluble guanylate cyclase. This effect of ET appears to be mediated by activation of ETB receptors and may serve to modulate the contractile effects of ET.

Acetylcholine↗

PubMed1992

Inhibition of vasopressin-sensitive cAMP accumulation by alpha 2-adrenoceptor agonists in collecting tubules is species dependent.

The ability of alpha 2-adrenoceptor agonists to inhibit vasopressin (VP)-stimulated cAMP accumulation in collecting tubules and to inhibit the antidiuretic effect of VP in rats is clearly established. However, in other species, such as the dog, alpha 2-adrenoceptor-induced inhibition of VP action has not been convincingly demonstrated. In the present study, we examined the effects of epinephrine and other alpha 2-adrenoceptor agonists on VP-stimulated cAMP accumulation in inner medullary collecting tubule cells and/or cortical collecting tubules from a number of species. Epinephrine, oxymetazoline, clonidine, and guanabenz inhibited VP-induced cAMP formation in rat inner medullary collecting tubule cells with IC50s ranging from 10 to 30 nM. However, epinephrine or guanabenz had no effect on VP-stimulated cAMP formation in cells from dog, pig, rhesus monkey, or human inner medulla. Similarly, epinephrine inhibited VP-induced cAMP accumulation in cortical collecting tubules dissected from rat kidneys but not from dog or rabbit kidneys. We conclude that there is a marked species difference in the ability of alpha 2-adrenoceptor agonists to inhibit VP-induced cAMP formation at the tubular level. This may explain the difficulty in demonstrating an alpha 2-adrenoceptor agonist-induced inhibition of VP action in other species such as dog and man.

Adrenergic alpha-Agonists↗

PubMed1992

Identification of endothelin receptor subtypes in human renal cortex and medulla using subtype-selective ligands.

High affinity and high density endothelin (ET)-binding sites were identified in membranes prepared from human kidney cortex and medulla. Saturation binding experiments performed in membranes prepared from cortex and medulla using [125I]ET-1 and [125I]ET-3 revealed that the proportion of [125I]ET-3-binding sites was 30-35% less than that of [125I]ET-1-binding sites. The apparent dissociation constants and maximum binding for [125I]ET-1 and [125I]ET-3 to membranes from cortex were 91 +/- 5 pM and 165 +/- 10 fmol/mg protein, and 117 +/- 9 pM and 110 +/- 7 fmol/mg protein, respectively, whereas in medulla they were 139 +/- 10 pM and 360 +/- 11 fmol/mg protein, and 142 +/- 11 pM and 245 +/- 15 fmol/mg protein, respectively. In the presence of 10 nM sarafotoxin-6c, which is selective for ETB receptors, [125I]ET-1 binding was decreased by 65-70%, whereas [125I]ET-3 binding was totally abolished, suggesting that 65-70% of [125I]ET-1 binding and 100% of [125I]ET-3 binding was to ETB receptors. This was further confirmed by the use of a cyclic pentapeptide [cyclo(D-Trp,D-Asp,L-Pro, D-Val,L-Leu)] (BQ123), which is selective for ETA receptors. In the presence of 1 microM BQ123, [125I]ET-1 binding was decreased by 25-30%, whereas [125I]ET-3 binding was unaffected, confirming that 30-35% of ET receptors belong to the ETA subtypes, and that [125I]ET-1 bound to both ETA and ETB receptors with the same high affinity, but [125I]ET-3 bound only to ETB receptors with high affinity. These results suggest that human kidney cortex and medulla contain ETA and ETB receptors in a ratio of 30:70, and that sarafotoxin-6c and BQ123 are valuable tools in identifying the subtype of ET receptors in various tissues.

Cell Membrane↗

PubMed1992

Knowledge about aging and Alzheimer's disease among baccalaureate nursing students.

Alzheimer's disease (AD) is a debilitating disease that poses many physical, social, psychological, and management problems for family and professional caregivers. Nursing students' ability to meet this challenge was measured using Palmore's (1988) Facts on Aging Quiz, Version 2 (FAQ2) and the Alzheimer's Disease Knowledge (ADK) Test developed by Dieckmann, Zarit, Zarit, and Gatz (1988). No significant difference in ADK Test scores was found for students who had previous personal or educational experiences with AD. However, older students, seniors, and those who reported knowing more about AD had significantly better scores on the ADK Test. Knowledge about AD was not found to be related to knowledge of aging, and subjects as a group were found to exhibit a negative bias toward the elderly as measured by Palmore's FAQ2.

Adult↗

PubMed1992

Pharmacological characterization of the nonpeptide angiotensin II receptor antagonist, SK&F 108566.

The angiotensin II (AII) antagonist activity of (E)-alpha-[[2-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5- yl]methylene]-2-thiophenepropanoic acid (SK&F 108566), was examined in a number of in vitro and in vivo assays. In rat and human adrenal cortical membranes, SK&F 108566 displaced specifically bound [125I]AII with IC50 of 9.2 and 3.9 nM, respectively. SK&F 108566 also inhibited [125I]AII binding to human liver membranes (IC50 = 1.7 nM) and to rat mesenteric artery membranes (IC50 = 1.5 nM). In rabbit aortic smooth muscle cells, SK&F 108566 caused a concentration-dependent inhibition of AII-induced increases in intracellular Ca++ levels. In rabbit aortic rings, SK&F 108566 produced parallel rightward shifts in the AII concentration-response curve without affecting the maximal contractile response. Schild analysis of the data yielded a KB value of 0.26 nM and a slope not different from 1, indicative of competition antagonism. SK&F 108566 had no effect on the contractile responses to KCl, norepinephrine or endothelin in rabbit aorta. In conscious normotensive rats, i.v. administration of SK&F 108566 (0.01-0.3 mg/kg) produced dose-dependent parallel shifts in the AII pressor dose-response curve. Administration of SK&F 108566 (3-10 mg/kg) intraduodenally or intragastrically to conscious normotensive rats resulted in a dose-dependent inhibition of the pressor response to AII (250 ng/kg, i.v.). At 10 mg/kg, i.d., significant inhibition of the pressor response to AII was observed for 3 hr. In this same rat model, SK&F 108566 had no effect on base-line pressure or on the pressor response to norepinephrine or vasopressin. The data demonstrate that SK&F 108566 is a potent, highly selective, competitive nonpeptide AII antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylates↗

PubMed1992

The antihypertensive effect of the angiotensin II receptor antagonist DuP 753 may not be due solely to angiotensin II receptor antagonism.

The angiotensin II (AII) receptor antagonist, DuP 753 (10 mg/kg intraduodenal), produced a sustained and long-lasting antihypertensive effect in conscious renin-dependent hypertensive rats. Blood pressures were still reduced markedly 24 to 72 hr after administration of a single dose of DuP 753. However, pressor responses elicited by either angiotensin I or AII were not blocked at these times despite the continued antihypertensive effect of DuP 753. In a model of orthostatic hypotension, DuP 753 and the selective alpha-1 adrenoceptor antagonist prazosin produced a marked orthostatic hypotension response in renin-dependent hypertensive rats as demonstrated by potentiation of the decrease in blood pressure induced by a 90 degrees tilt. The nonpeptide AII receptor antagonist SK&F 108566 (10 mg/kg intraduodenal) did not produce orthostatic hypotension and the angiotensin converting enzyme inhibitor enalapril produced only a slight orthostatic response to tilting. In conscious spontaneously hypertensive rats (SHR), allowed 3 to 4 days to recover from surgery, administration of either enalapril (1 mg/kg i.v.) or SK&F 108566 (10 mg/kg i.v.) did not significantly effect blood pressure. In SHR tested within 24 hr of surgery, enalapril was effective in lowering blood pressure. In contrast, in surgically recovered SHR, DuP 753 (10 mg/kg i.v.) produced an antihypertensive effect that was slow in onset, sustained and extremely long in duration. Blood pressures did not return to predrug levels until 48 hr after administration of DuP 753. Stimulation of the thoracolumbar sympathetic outflow in pithed rats produced frequency-dependent pressor responses that were significantly potentiated by continuous infusion of a subpressor dose of AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylates↗

PubMed1992

Characterization of renal angiotensin II receptors using subtype selective antagonists.

Two angiotensin II (AII) receptor subtypes, AT1 and AT2, have recently been identified based on their relative affinities for selective peptide and nonpeptide antagonists. In the present study we used various AII peptide analogs, the AT1 subtype selective antagonists, DuP 753 and SK&F 108566, and the AT2 subtype selective antagonists, WL-19 and CGP 42112A, to determine whether AII receptor subtypes exist in the kidney. In agreement with previous studies, octapeptide (Sar1,Ile8-AII) and heptapeptide (AIII and Ile8-AIII) AII analogs displaced [125I]AII bound to rat glomerular membranes with similar affinities. However, in membranes derived from cortical tubules and the outer medulla, the heptapeptide analogs were 20-fold less potent in competing with [125I]AII binding than octapeptide analogs. The AT1 subtype selective nonpeptide AII antagonists, DuP 753 and SK&F 108566, totally displaced [125I]AII binding from all three membrane preparations in a monophasic manner with IC50 values in the 5 to 30 nM range. The AT2 selective peptide antagonist, CGP 42112A, had a low affinity in AII three membranes (IC50 = 450-1050 nM), whereas the nonpeptide AT2 selective antagonist, WL-19, had no activity at concentrations up to 10 microM. Dithiothreitol and the nonhydrolyzable GTP analog, 5'-guanylyl-imidodiphosphate, inhibited AII binding to all three membrane preparations. Based on these results, we conclude that the AII receptors located on glomeruli, tubules and in the outer medulla belong to the AT1 subtype, and that the physiologically important renal actions of AII are mediated through activation of AT1 receptors.

Acrylates↗

PubMed1991

Secretion of human epidermal growth factor from Saccharomyces cerevisiae using synthetic leader sequences.

We have investigated different leader sequences for their ability to direct the efficient secretion of human epidermal growth factor (hEGF) from Saccharomyces cerevisiae. We designed a consensus signal sequence which directs secretion of hEGF from yeast as efficiently as the yeast invertase signal sequence. However, secretion is increased over fivefold by the introduction, after the signal sequence, of a synthetic 19-amino acid (aa) pro-sequence containing a cleavage recognition site for the KEX2 protease. Even in the absence of an Asn-linked glycosylation site, secretion of hEGF using the synthetic prepro-leader was as efficient as that directed by the alpha-factor leader. The role of the KEX2 protease cleavage site was investigated by mutation of the yeast alpha-factor KEX2 site (cleavage after Lys-Arg). Cleavage was obtained with the following order of efficiency, Lys-Arg greater than Pro-Arg greater than Asp-Arg, although the sequence context was also found to affect efficiency.

Amino Acid Sequence↗

PubMed1991

Structure-function relationships in human epidermal growth factor studied by site-directed mutagenesis and 1H NMR.

In order to elucidate the mechanism of interaction between human epidermal growth factor (EGF) and its receptor, selected variants of EGF, differing by single amino acid substitutions, have been made by site-directed mutagenesis. The receptor affinity of these mutants was determined by a receptor binding competition assay, and the effects of the substitution on the structure of the protein were assessed by 1H nuclear magnetic resonance techniques. Various substitutions of Arg-41 resulted in substantial reduction in receptor affinity of EGF whereas change of Tyr-13 did not affect binding to the receptor. The 1H resonances of all nonexchangeable protons of the Tyr-13----Leu, Arg-41----His, and Leu-47----Glu variants were assigned and compared in order to assess the structural integrity of these mutants, which possess very different spectral and biological properties. In the case of the Leu-47----Glu mutant, only minor localized spectral changes were observed, confirming that the tertiary structure of the protein is preserved upon mutation. In contrast, for both the Arg-41----His and Tyr-13----Leu variants, significant and strikingly similar spectra changes were observed for many residues located far away from the mutated residues. This implies that similar structural alterations have taken place in both proteins, an idea further supported by hydrogen-exchange experiments where the exchange rates of hydrogen-bonded amide protons for both the Tyr-13----Leu and the Arg-41----His mutants were found to be about 4 times faster than in the wild-type protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Structural and functional studies of the endothelial activation antigen endothelial leucocyte adhesion molecule-1 using a panel of monoclonal antibodies.

We have produced a panel of mAb to the endothelial activation Ag endothelial leucocyte adhesion molecule-1 (ELAM-1), using both a conventional immunization protocol and one involving immunosuppression. By constructing ELAM-1 mutants we have demonstrated that seven of these antibodies recognize epitopes within the lectin domain of ELAM-1 and that one binds within the complement regulatory protein domains. These studies also suggest that the EGF-like domain is important in maintaining the conformation of the neighbouring lectin domain. In functional studies, U937 cells bound to Cos cells expressing either ELAM-1 or ELAM-1 with the complement regulatory protein domains deleted. No adhesion was observed to Cos cells expressing ELAM-1 mutants lacking either the lectin or EGF-like domains. The fact that antibodies directed against the lectin domain can inhibit adhesion suggest that this domain is directly involved in cell binding.

Antibodies, Monoclonal↗

PubMed1991

Two PDGF-B chain residues, arginine 27 and isoleucine 30, mediate receptor binding and activation.

PDGF may be involved in the pathogenesis of a variety of disorders including atherosclerosis and certain types of cancer. There is currently little understanding of the molecular structure of PDGF and of the critical amino acid residues involved in receptor binding and cell activation. Two such PDGF-B chain residues, arginine 27 and isoleucine 30, have been identified by a site-directed mutagenesis programme. Substitutions in these positions can lead to PDGF mutants defective in both receptor affinity and cell activation as judged by displacement of [125I]PDGF-BB, mitogenic assay and inositol lipid turnover. Circular dichroism and fluorescence spectroscopy show that such mutations do not disrupt the structure of PDGF.

3T3 Cells↗

PubMed1991

Marked increase in the teratogenicity of the combined administration of the industrial solvent 2-methoxyethanol and radiofrequency radiation in rats.

Limited published animal research reports synergistic teratogenic effects following combined hyperthermia (induced by elevated ambient temperature) and administration of chemical teratogens. Radiofrequency (RF) radiation is widely used in occupational environments. Since RF radiation also elevates the body temperature of, and is teratogenic to, exposed animals, concurrent RF radiation and chemical agent administration may enhance teratogenicity. The present exploratory study, consisting of preliminary dose-finding studies and the primary study, was designed to investigate whether concurrent exposure of rats to RF radiation and the industrial solvent 2-methoxyethanol (2ME) can enhance the developmental toxicity of either agent acting alone. Preliminary dose-finding studies using small numbers of rats investigated the ability of various RF radiation conditions and doses of 2ME to produce external malformations (primarily of the paws) when administered on gestation day 13. Based on these preliminary studies, RF radiation exposure [sufficient to elevate rectal temperature to 42.0 degrees C (4 degrees C above normal for rats) for 30 min] and 2ME administration (150 mg/kg) were selected for the primary study. In the primary study, groups of 18 to 27 pregnant rats were administered RF radiation exposure and distilled water gavage, 2ME gavage and sham RF exposure, RF radiation exposure and 2ME gavage concurrently, or sham RF exposure and distilled water gavage. Pregnant rats were sacrificed on gestation day 20, and the offspring were examined for external malformations. Combined exposures enhanced the adverse effects produced by either experimental agent alone (no malformations were detected in the double sham group). Mean fetal malformations/litter increased from 14% after 2ME and sham RF (15/26 litters affected, with an average of 2 fetuses/litter malformed) and 30% after RF radiation and water gavage (10/18 litters affected, with an average of 4 fetuses/litter malformed), to 76% after the combined treatment (18/18 litters affected, with an average of 12 fetuses/litter malformed). In addition to a significant increase in the frequency of malformations, the severity of malformations also was enhanced by the combination treatment (on a relative severity ranking scale, the 2ME severity score was less than 1, the RF score was 3, and the combination score was 6). This study provided evidence of synergism between RF radiation and 2ME administration, but additional research will be required to characterize the extent of synergism between these two agents. Potential interactive effects between chemical and physical agents need to be investigated to determine the extent to which such interactions should impact occupational exposure standards.

Animals↗

PubMed1991

Modulation of vasopressin antidiuretic action by alpha 2-adrenoceptors is species specific.

There is evidence in the rat that stimulation of renal alpha 2-adrenoceptors modulates vasopressin antidiuretic action and vasopressin-stimulated adenylate cyclase activity. In the present study, we tested the ability of various alpha 2-adrenoceptor agonists to antagonize vasopressin-induced antidiuresis in the conscious hydrated dog and to inhibit vasopressin-induced adenosine 3',5'-cyclic monophosphate (cAMP) generation in rat and dog cortical collecting tubules. Vasopressin infusion (0.01 ng.kg-1.min-1) in five dogs resulted in a decrease in free water clearance from 2.90 +/- 0.42 to -0.34 +/- 0.08 ml/min. The vasopressin receptor antagonist SKF 105494 inhibited this response. Administration of norepinephrine (0.5 microgram.kg-1.min-1) or clonidine (20 micrograms/kg), however, failed to alter the vasopressin-induced antidiuresis. In vitro studies demonstrated that epinephrine caused a dose-dependent reduction in vasopressin-stimulated cAMP levels in cortical collecting tubules from the rat (50% effective concentration 32 nM) but not from the dog. The data indicate that there is a species difference in alpha 2-adrenoceptor modulation of vasopressin action.

Adenylyl Cyclases↗

PubMed1991

Relaxation of renal arterioles by parathyroid hormone and parathyroid hormone-related protein.

The effects of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) on renal arteriolar tone and proximal tubule adenylate cyclase were examined. In both afferent and efferent arterioles, PTH produced concentration-dependent relaxation of norepinephrine-induced tone with EC50 values of 8.7 and 9.9 nmol/l, respectively. PTHrP also produced relaxations that were indistinguishable from PTH. In proximal convoluted tubules PTH and PTHrP stimulated adenylate cyclase to the same extent and with similar potencies. The PTH antagonist, bPTH(7-34), totally blocked PTH-induced arteriolar relaxation but had no effect on proximal tubule adenylate cyclase. The results demonstrate that PTH and PTHrP are potent relaxants of glomerular arterioles and that PTH receptors present on the renal microvasculature may differ from those present on proximal tubules.

Adenylyl Cyclase Inhibitors↗

PubMed1991

The water diuretic effect of the alpha-2 adrenoceptor agonist, AGN 190851, is species-dependent.

The effect of the novel alpha-2 adrenoceptor agonist, AGN 190851, was evaluated for its diuretic action in the rat, dog and cynomolgus monkey and its ability to inhibit vasopressin-stimulated cyclic AMP accumulation in rat and dog cortical collecting tubules in vitro. The data indicate that in the rat, AGN 190851 resulted in a dose-dependent water diuresis, which was accompanied by an increase in blood pressure and osmolar clearance. In addition, AGN 190851 resulted in a dose-dependent inhibition of vasopressin-stimulated cyclic AMP accumulation in rat cortical collecting tubules in vitro. In contrast, AGN 190851 was unable to cause either a water diuresis in conscious dogs or inhibit vasopressin-stimulated adenylate cyclase activity in canine tissue in vitro. In the lightly anesthetized cynomolgus monkey, AGN 190851 also failed to alter renal function significantly. Administration of the vasopressin receptor antagonist, SK&F 105494, to either dogs or cynomolgus monkeys demonstrated that antagonism of the vasopressin V2 receptor could result in a brisk water diuresis in both species. The data demonstrate that alpha-2 adrenoceptors can functionally antagonize vasopressin antidiuretic activity in the rat, but not in the dog or cynomolgus monkey.

Adrenergic alpha-Agonists↗

PubMed1991

Calcitonin gene-related peptide stimulates adenylate cyclase and relaxes intracerebral arterioles.

The effects of calcitonin gene-related peptide (CGRP) on lumen diameter and adenylate cyclase activity in isolated intracerebral arterioles were examined. CGRP produced a concentration-dependent relaxation of spontaneous tone developed by the arterioles with an EC50 value of 3.9 x 10(-9) M. Calcitonin, as well as substance P, which is frequently colocalized with CGRP, had no effect on arteriolar tone. CGRP also relaxed arterioles contracted with the thromboxane mimetic, U-44619, yielding an EC50 value of 3 x 10(-9) M. The CGRP fragment, human CGRP(8-37), antagonized CGRP-induced relaxation in a noncompetitive manner. Adenylate cyclase activity in single arterioles was stimulated by CGRP, but not by substance P, in a concentration-dependent fashion. Half maximal stimulation occurred at 8 x 10(-9) M, whereas maximum stimulation (2.5-fold over basal) occurred at 10(-7) M. CGRP(8-37) inhibited CGRP-stimulated adenylate cyclase activity over a concentration range of 10(-9) to 10(-5) M. The results demonstrate that CGRP stimulates adenylate cyclase activity and is a potent vasodilator of small parenchymal cerebral arterioles in vitro and may play an important role in the regulation of cerebral blood flow.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1990

Neuropeptide Y inhibits cAMP accumulation in renal proximal convoluted tubules.

The effect of neuropeptide Y (NPY) on cAMP accumulation in various segments of the rabbit nephron was examined. NPY inhibited parathyroid hormone-stimulated cAMP accumulation in the proximal convoluted tubule in a concentration-dependent manner. NPY also inhibited forskolin-stimulated cAMP production in this segment of the nephron. In contrast, NPY had no effect on parathyroid hormone or forskolin-stimulated cAMP accumulation in the proximal straight tubule. Similarly, NPY had no effect on forskolin-stimulated cAMP levels along the rest of the nephron. These results are consistent with previous studies which have localized NPY receptors to the proximal convoluted tubule, and suggest that NPY via its effects on cAMP metabolism may play a role in proximal tubule transport.

Animals↗