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Biomedical subjects

M S Parker

Publications and source records attributed to M S Parker.

At least 19 recordsLinked to original sources
PubMed2002

Agonist internalization by cloned Y1 neuropeptide Y (NPY) receptor in Chinese hamster ovary cells shows strong preference for NPY, endosome-linked entry and fast receptor recycling.

In Chinese hamster ovary (CHO) cells expressing the cloned guinea-pig Y1 receptor, the saturable, receptor-linked internalization of NPY (NPY)-related peptides showed the rank order of human/rat neuropeptide Y (hNPY)>pig/rat peptide YY (pPYY)>=(Pro(34))human PYY>(Leu(31),Pro(34))hNPY>(Leu(31),Pro(34))hPYY>>BVD-11 (a selective Y1 antagonist). All agonists accessed similar numbers of Y1 sites in particulates from disrupted cells, with relatively small affinity variation. The rate of internalization could significantly depend on the overall interactivity of the agonist peptide (reflected in sensitivity to chaotropic agents, as well as in the level of non-saturable binding and internalization). Concentration-dependent inhibition of the agonist-driven CHO-Y1 internalization was found with filipin III (a cholesterol-complexing macrolide), and confirmed with inhibitors of clathrin lattice formation, phenylarsine oxide (PAO) and sucrose. In the concentration range affecting Y1 internalization, none of the above treatments or agents significantly alter agonist affinity for Y1 cell surface or particulate receptors. Largely similar responses to the above inhibitors were observed in CHO-Y1 cells for internalization of human transferrin. Internalization of CHO-Y1 receptor apparently is driven by NPY in strong preference to other naturally encountered agonists. At 37 degrees C, most of the internalized receptor is rapidly recycled through endosome-like membrane elements, detectable in Percoll gradients.

Animals↗
PubMed2001

Blockade of pancreatic polypeptide-sensitive neuropeptide Y (NPY) receptors by agonist peptides is prevented by modulators of sodium transport. Implications for receptor signaling and regulation.

Ligand binding to rodent pancreatic polypeptide-responding neuropeptide Y (NPY) receptors (here termed PP/NPY receptors), or to cloned Y4 or Y5 receptors, is selectively inhibited by amiloride, peptide or alkylating modulators of sodium transport. The PP/NPY and Y4 receptors are also selectively blocked by human or rat pancreatic polypeptide (PP) and the blocking peptides are not dissociated by high concentrations of alkali chlorides (which restore most of the binding of subtype-selective agonists to Y1 and Y2 sites). The PP/NPY receptors could also be blocked by NPY and related full-length peptides, including Y1-selective agonists (IC50 300-400 pM). The cloned Y(4) receptors from three species are much less sensitive to NPY or PYY. The sensitivity of both the PP/NPY sites and the Y(4) sites to Y2-selective peptides is quite low. The ligand attachment to PP/NPY sites is also very sensitive to peptidic Y1 antagonist ((Cys31,NVal34NPY27-36))2, which however blocks these sites at much higher molarities. Blockade of PP/NPY and Y4 sites by agonist peptides can be largely prevented by N5-substituted amiloride modulators of Na+ transport, and by RFamide NRNFLRF.NH2, but not by Ca2+ channel blockers, or by inhibitors of K+ transport. Protection of both PP/NPY and Y4 sites against blockade by human or rat pancreatic polypeptide is also afforded by short N-terminally truncated NPY-related peptides. The above results are consistent with a stringent and selective activity regulation for rabbit PP/NPY receptor(s) that may serve to differentiate agonists and constrain signaling, and could involve transporter-like interactants.

Animals↗
PubMed2001

Cloned neuropeptide Y (NPY) Y1 and pancreatic polypeptide Y4 receptors expressed in Chinese hamster ovary cells show considerable agonist-driven internalization, in contrast to the NPY Y2 receptor.

Guinea-pig neuropeptide Y1 and rat pancreatic polypeptide Y4 receptors expressed in Chinese hamster ovary cells were internalized rapidly upon attachment of selective peptide agonists. The Y1 and Y2, but not the Y4, receptor also internalized the nonselective neuropeptide Y receptor agonist, human/rat neuropeptide Y. The internalization of guinea-pig neuropeptide Y2 receptor expressed in Chinese hamster ovary cells was small at 37 degrees C, and essentially absent at or below 15 degrees C, possibly in connection to the large molecular size of the receptor-ligand complexes (up to 400 kDa for the internalized fraction). The rate of intake was strongly temperature dependent, with essentially no internalization at 6 degrees C for any receptor. Internalized receptors were largely associated with light, endosome-like particulates. Sucrose dose-dependently decreased the internalization rate for all receptors, while affecting ligand attachment to cell membrane sites much less. Internalization of the Y1 and the Y4 receptors could be blocked, and that of the Y2 receptor significantly inhibited, by phenylarsine oxide, which also unmasked spare cell-surface receptors especially abundant for the Y2 subtype. The restoration of Y1 and Y4 receptors after agonist peptide pretreatment was decreased significantly by cycloheximide and monensin. Thus, in Chinese hamster ovary cells the Y1 and Y4 receptors have much larger subcellular dynamics than the Y2 receptor. This differential could also hold in organismic systems, and is comparable with the known differences in internalization of angiotensin, bradykinin, somatostatin and opioid receptor subtypes.

Alkylating Agents↗
PubMed2001

Making the transition: the role of helical CT in the evaluation of potentially acute thoracic aortic injuries.

OBJECTIVE: The purpose of this study was to show that helical CT could be used at our center in lieu of routine aortography to examine patients who have had serious blunt chest trauma. We also wanted to assess the potential savings of using CT to avoid unnecessary aortography. MATERIALS AND METHODS: The institutional review board approved the parallel imaging-CT immediately followed by aortography-of patients presenting with blunt chest trauma between August 1997 and August 1998. To screen patients for potential aortic injuries, we performed parallel imaging on 142 patients, and these patients comprised our patient population. CT examinations of the patients were reviewed for signs of injury by radiologists who were unaware of each other's interpretations and the aortographic results. Findings of CT examinations were classified as negative, positive, or inconclusive for injury. Aortography was performed immediately after CT. The technical and professional fees for both transcatheter aortography and helical CT were also compared. RESULTS: Our combined kappa value for all CT interpretations was 0.714. The aortographic sensitivity and negative predictive value were both 100%. Likewise, the sensitivity and negative predictive value of CT were 100%. The total costs of performing aortography were estimated at approximately $402,900, whereas those for performing helical CT were estimated at $202,800. CONCLUSION: Helical CT has a sensitivity and negative predictive value equivalent to that of aortography. Using CT to eliminate the possibility of mediastinal hematoma and to evaluate the cause of an abnormal aortic contour in a trauma patient allows us to use aortography more selectively. Avoiding the performance of unnecessary aortography will expedite patient care and reduce costs. We report the results of our experience with CT and how our center successfully made this transition in the initial examination of patients with serious thoracic trauma.

Acute Disease↗
PubMed2000

Ligand association with the rabbit kidney and brain Y1, Y2 and Y5-like neuropeptide Y (NPY) receptors shows large subtype-related differences in sensitivity to chaotropic and alkylating agents.

The binding to rabbit kidney or hypothalamic particulates of the subtype-selective neuropeptide Y (NPY) receptor ligands [125I](Leu31,Pro34)hPYY (as Y1 site label at 2 nM human pancreatic polypeptide (hPP)), [125I]-hPYY(3-36) (Y2 label), and [125I]-hPP (Y5 label) displayed great differences in sensitivity to alkylators and chaotropic agents. Sensitivity to a nonionic chaotrope, urea, was much higher for the Y1 binding than for the Y5-like binding or the Y2 binding. The non-selective alkylator N-ethylmaleimide (NEM) and several alkylators selective for aminergic receptors were much more efficacious against the Y1 relative to the Y2 binding. Similar differences could be confirmed with the attachment of Y1 and Y2-selective tracers to CHO cells expressing the cloned guinea-pig Y1 or Y2 receptors. The Y5-like binding was quite insensitive to NEM, but sensitive to chloroethylclonidine (CEC) and prazobind, which were less potent at the Y1, and especially at the Y2 site. The unrestricted-access alkylator 2-aminoethyl methanethiosulfonate inhibited the binding to all subtypes, while the restricted-access agent 2-(trimethylammonium)ethylmethanethiosulfonate poorly inhibited the Y5-like binding, or the guanine nucleotide-insensitive Y2 binding. These results are compatible with an active conformation of the Y5-like site dependent on maintenance of a shared hydrophobic cavity. The Y2 sites resistant to guanosine polyphosphates and restricted-access alkylators were detected mainly in particulates slowly solubilized by cholate at 0-5 degrees C; these sites could be clustered.

Alkylating Agents↗
PubMed2000

Upregulation of pancreatic polypeptide-sensitive neuropeptide Y (NPY) receptors in estrogen-induced hypertrophy of the anterior pituitary gland in the Fischer-344 rat.

Implants of diethylstilbestrol inducing anterior pituitary prolactinomas in female Fischer-344 rats produced a considerable elevation of high-affinity binding of either rat or human pancreatic polypeptide (hPP). No comparable upregulation of high-affinity binding sites was noted for the ligand [125I](Leu31,Pro34)hPYY (LP-PYY) (masked by 2 nM hPP to force selectivity for the Y1 sites), or of the Y2-selective ligand [125I]hPYY(3-36). The Y5-like sites displayed the rank order of potency of hPP = rPP, hNPY, LP-PYY > pPYY(1-36) > hNPY(2-36) > hPYY(3-36) >> aPP, similar to the previously described rabbit kidney or hypothalamic Y5-like receptors. The PP binding in the anterior pituitary was not sensitive to the Y1-selective non-peptidic antagonist BIBP-3226. The PP binding was highly sensitive to alkali metal cations, and to a N5-substituted amiloride antagonist of sodium transport, but not to a C2-guanido substituted amiloride antagonist of sodium channels. The binding was also sensitive to phospholipase C antagonist U-73122, and to alkylating alpha-adrenergic agonist chloroethylclonidine. Lactotrophs isolated in Percoll gradients after enzymic dispersion of the anterior pituitary gland retained the high-affinity PP binding. Following removal of estrogen implants, the hPP binding sites decreased to very low levels within 3 days, in parallel to the decrease of plasma prolactin.

Animals↗
PubMed2000

Binding sites for human interferon-gamma in protocerebrum and hemolymph of tobacco hornworm (Manduca sexta) larvae differ in sensitivity to polycationic peptides.

We have recently characterized specific binding sites for human interferon-gamma on particulates prepared from the protocerebrum and hemolymph of tobacco hornworm larvae, Manduca sexta ¿(Parker, M.S., Ourth, D.D., 1999. Comp. Biochem. Physiol. B 122, 155-163). The sensitivity to sulfated polysaccharides indicated an involvement of oligobasic epitopes of hIFN-gamma in the binding. In the present study, we found that polycationic peptides inhibited the binding of [125I]hIFN-gamma to particulates from either the hemolymph or the protocerebrum of Manduca sexta larvae. With amino acid homopolymers, the rank order of potency was poly-L-lysine > poly-L-arginine >> poly-L-ornithine, while the acidic side chain polymer poly-L-aspartate was not inhibitory. However, the potency of all polycationic peptides was at least three-fold greater at the hemolymph particulates. Also, acidic polysaccharides such as heparin were much more efficacious in the inhibition of hIFN-gamma binding to hemolymph relative to protocerebral particulates. The peptide polycations inhibited the binding of [125I](Leu31,Pro34)human peptide YY, a ligand selective for the Y1 subtype of the neuropeptide Y receptor, to rabbit kidney or to parietal cortex particulates with the expected rank order of poly-L-arginine > poly-L-lysine >> poly-L-ornithine, and with little cross-tissue difference in affinity. The selectivity observed with M. sexta particulates indicates a preferential involvement of oligobasic lysine-rich C-terminal sequences of IFN-gamma, while large insect tissue-related affinity differences point to involvement of diverse oligoacidic sequences in binding to protocerebrum and hemolymph sites. This study provides evidence for the presence of molecules in lepidopteran larvae that are similar in structure to vertebrate co-receptors of IFN-gamma, and adds to the characterization of these binding sites.

Amino Acids↗
PubMed2000

Functional expression of three P2X(2) receptor splice variants from guinea pig cochlea.

ATP has been suggested to act as a neurotransmitter or a neuromodulator in the cochlea. The responses to ATP in different cell types of the cochlea vary in terms of the rate of desensitization and magnitude, suggesting that there may be different subtypes of P2X receptors distributed in the cochlea. Recently three ionotropic P2X(2) receptor splice variants, P2X(2-1), P2X(2-2), and P2X(2-3,) were isolated and sequenced from a guinea pig cochlear cDNA library. To test the hypothesis that these different splice variants could be expressed as functional homomeric receptors, the three P2X(2) receptor variants were individually and transiently expressed in human embryonic kidney cells (HEK293). The biophysical and pharmacological properties of these receptors were characterized using the whole cell patch-clamp technique. Extracellular application of ATP induced an inward current in HEK293 cells containing each of the three splice variants in a dose-dependent manner indicating the expression of homomeric receptors. Current-voltage (I-V) relationships for the ATP-gated current show that the three subtypes of the P2X(2) receptor had a similar reversal potential and an inward rectification index (I(50 mV)/I(-50 mV)). However, the ATP-induced currents in cells expressing P2X(2-1) and P2X(2-2) variants were large and desensitized rapidly whereas the current in those cells expressing the P2X(2-3) variant was much smaller and desensitized slower. The order of potency to ATP agonists was 2-MeSATP > ATP > alpha,beta -MeATP for all three expressed splice variants. The ATP receptor antagonists suramin and PPADS reduced the effects of ATP on all three variants. Results demonstrate that three P2X(2) splice variants from guinea pig cochlea, P2X(2-1), P2X(2-2), and P2X(2-3), can individually form nonselective cation receptor channels when these subunits are expressed in HEK293 cells. The distinct properties of these P2X(2) receptor splice variants may contribute to the differences in the response to ATP observed in native cochlear cells.

Adenosine Triphosphate↗
PubMed2000

FMRFamides exert a unique modulation of rodent pancreatic polypeptide sensitive neuropeptide Y (NPY) receptors.

FMRFamide and related peptides (RFamides) were found to inhibit the association binding of iodinated human pancreatic polypeptide ([125I]hPP) to Y5-like neuropeptide Y (NPY) receptor in rodent tissues. An allosteric regulation of the activity of the rodent kidney PP-sensitive neuropeptide Y (NPY) receptor by RFamides was indicated by potency decrease with particle concentration in the inhibition of the association binding of 125I-labeled human pancreatic polypeptide (hPP) by RFamides at rabbit kidney membranes. The competition by C-terminal hexapeptide of hPP (LTRPRY.NH2) did not show such affinity change. The steady-state binding of hPP showed little sensitivity to any of the RFamides tested. The Y1-selective binding of [125I][Leu31,Pro34]hPYY (at 2 nM hPP) was much less sensitive to RFamides than the binding of [125I]hPP, albeit with some differences across tissue or cell types. The binding of Y2-selective agonist 125I-labeled human peptide YY (3-36) was quite insensitive to RFamides. The presence of a unique component in the inhibition of hPP binding by RFamides was further indicated by a degree of antagonism with phospholipase C inhibitor U-73122, and by an only limited cooperation with a N5-amiloride compound, and with alkylator chloroethylclonidine. Change of the chirality of individual residues in the FMRFamide molecule produced a significant reduction of inhibitory potency only with D-Phe in the C-terminal position. Substitution of the (C-3) L-Met by L-Leu greatly increased the inhibitory potency of RFamides relative to otherwise identical congeners. RFamides could act both as ligands of membrane neighbors of the PP receptor, and as competitors of Y5-like NPY receptor epitopes that accommodate the C-terminal aspects of agonist peptides.

Amino Acid Sequence↗
PubMed1999

Characterization of rabbit kidney and brain pancreatic polypeptide-binding neuropeptide Y receptors: differences with Y1 and Y2 sites in sensitivity to amiloride derivatives affecting sodium transport.

Sites sensitive to human and rat pancreatic polypeptides (hPP and rPP) accounted for more than 30% of the specific binding of [125I](Leu31,Pro34) human peptide YY (LP-PYY) in particulates from rabbit kidney cortex, and about 10% of the specific binding in membranes from rabbit hypothalamus. The binding of [125I]hPP or [125I]rPP showed a high-affinity displacement with either hPP, rPP, LP-PYY, neuropeptide Y or peptide YY (Ki below 50 pM for all), while being quite insensitive to Y2-selective ligands. The PP binding had a high sensitivity to alkali cations and inhibitors of phospholipase C, very similar to that of LP-PYY binding 'masked' by excess cold hPP. However, as different from the Y1-like LP-PYY binding, but similar to the binding of the Y2-selective ligand [125I]human peptide YY(3-36) (hPYY(3-36)), the PP binding showed a low sensitivity to guanosine polyphosphates. The PP binding was much more sensitive to N5-substituted amiloride inhibitors of Na+ transport than the binding of LP-PYY, or that of hPYY(3-36). The inhibition of PP binding by N5-substituted amilorides was not enhanced by guanine nucleotides or by phospholipase C blockers. However, pairing of N5-substituted amilorides disproportionately increased the inhibition of hPP binding. Thus, in rabbit kidney or hypothalamus, the high-affinity PP-responding sites share some of the basic properties of the Y1 and Y2 sites, but are distinguished from both by a high sensitivity to compounds affecting sodium transport. These PP/NPY receptors could associate with membrane structures involved in the control of ion balance and osmotic responses.

Amiloride↗
PubMed1999

Specific binding of human interferon-gamma to particulates from hemolymph and protocerebrum of tobacco hornworm (Manduca sexta) larvae.

Specific binding sites for human interferon-gamma (hIFN-gamma) were found on particulates prepared from the hemolymph and protocerebrum of fifth-instar larvae of the tobacco hornworm, Manduca sexta. A portion of these sites could be solubilized in an active form by the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS). A well-defined specific binding was also associated with hemolymph particulate residue after solubilization by CHAPS. About one-half of [125I]hIFN-gamma binding could be displaced by heparin. The bound hIFN-gamma could be covalently cross-linked to the binding sites using disuccinylamide suberate, and the molecular weight range of these complexes was 200-800 kDa as determined by density gradient sedimentation and gel-exclusion chromatography. Only a small fraction of the hemolymph IFN-gamma binding could be competed by another mammalian cytokine, rat prolactin (rPRL), while there was no sensitivity to rat growth hormone. The small specific rPRL binding found in Manduca hemolymph showed an affinity similar to the prolactin sites found in the liver of pregnant rats. The detergent-insoluble Manduca hIFN-gamma binding was bimodal and similar in affinity distribution to the binding found with human platelet membranes (Kdiss range 0.1-2 nM). The detergent-solubilized IFN-gamma sites were homogenous, with a Kdiss of about 1.5 nM. The IFN-gamma binding sites in Manduca tissues may therefore include molecular species similar to the known invertebrate cytokine receptors and proteoglycan co-receptors.

Amino Acid Sequence↗
PubMed1999

Phosphorothioate oligodeoxynucleotides can selectively alter neuronal activity in the cochlea.

A growing body of evidence indicates that extracellular adenosine triphosphate (ATP) may have a major role in cochlear function. Antagonists of ionotropic ATP receptors (P2X2) have significant effects on cochlear potentials and distortion product otoacoustic emissions (DPOAEs). We tested whether antisense oligodeoxynucleotides (ODNs) would mimic the functional deficiencies induced by the ATP antagonists through binding to P2X2 ATP receptor mRNA and thereby reduce the number of ATP receptors expressed in the membrane of the cells. Both a phosphorothioate ODN (S-ODN) antisense and a phosphodiester ODN (P-ODN) antisense to the P2X2 sequence and random sense ODNs containing 21 nucleotides were administered chronically (7 days) to the guinea pig cochlea via the perilymph compartment. Sound evoked cochlear potentials (cochlear microphonic; summating potential; compound action potential of the auditory nerve, CAP; latency of the first negative peak in the CAP, N1 latency) and DPOAEs were monitored to assess the effects of the ODNs. Results indicate that the phosphorothioate derivatives of both the antisense and random sense ODNs suppressed the CAP and prolonged the N1 latency with no significant effect on the other parameters. The P-ODNs had no effect. Since both the antisense and random sense S-ODNs had the same effect, we conclude that the S-ODNs affected neuronal function in a manner that did not involve binding to the ATP receptor mRNA.

Adenosine Triphosphate↗
PubMed1998

Characterization of Y1, Y2 and Y5 subtypes of the neuropeptide Y (NPY) receptor in rabbit kidney. Sensitivity of ligand binding to guanine nucleotides and phospholipase C inhibitors.

The binding of two peptide YY/neuropeptide Y analogues selective for major subtypes of neuropeptide Y (NPY) receptors was compared in particulates from rabbit kidney cortex employing modulators of activity of G-proteins, phospholipase enzymes, and ion channels. The binding of (Leu31,Pro34)human peptide YY resembled the patterns observed previously for the brain tissue Y1 receptor, exhibiting a high sensitivity to monovalent cations, disulfide disruptors, guanosine polyphosphates and phospholipase C inhibitors. However, this binding was bimodal in response to human pancreatic polypeptide and to peptides selective for the Y2 subtype of the NPY receptor, displaying a large component pharmacologically similar to the brain Y5 receptor. This kidney Y5-like binding largely shared the sensitivity to monovalent cations, guanine nucleotides and phospholipase C inhibitors found for either the kidney or the brain Y1 receptor, and also was activated by Ca2+ ion. Both Y1- and Y5-like binding in the kidney displayed a uniformly low reactivity to a nonpeptidic Y1 antagonist, BIBP-3226, and to a receptor peptide mimetic, mastoparan analogue MAS-7. The kidney Y2 binding shared the low sensitivity to ionic environment observed for the brain Y2 subtype, and was only partially sensitive to guanine nucleotides or to MAS-7. The Y2 liganding had a sensitivity to phospholipase C inhibitors similar to the Y1/Y5 binding. This reactivity was retained in the fraction of the Y2 receptor persisting detergent solubilization in a high-affinity form, which, however, was activated rather than inhibited by G-protein agonists.

Alkylating Agents↗
PubMed1998

Novel variant of the P2X2 ATP receptor from the guinea pig organ of Corti.

ATP functions as a neurotransmitter and a neuromodulator in various tissues by acting on metabotropic (P2Y) and ionotropic (P2X) receptors. Evidence suggests that ATP activates P2X receptors on several cell types in the organ of Corti of guinea pig including outer hair cells (OHCs), Deiters' cells, Hensen's cells, pillar cells and inner hair cells (IHCs). Determining the sequence and structure of P2X receptors in guinea pig organ of Corti is important for understanding the function of ATP in the cochlea. We screened a guinea pig organ of Corti cDNA library for P2X2 ATP receptors using rat P2X2 cDNA as a probe. We sequenced three P2X2 variants which were found to be abundant in this library. One is a novel P2X2 isoform (P2X2-3) created by a retained intron coding for an additional 27 amino acids (81 bp) in the putative extracellular domain. We have also sequenced a variant (P2X2-2) that lacks both the 81-bp sequence and a 192-bp sequence in the 3' intracellular domain. A third variant (P2X2-1) contains the intracellular 192-bp sequence but not the extracellular 81-bp sequence found in P2X2-3. The multiple transcripts arise from alternative intron and exon splicing events. In situ hybridization with a probe common to the three variants localized P2X2 to many of the cells of the organ of Corti.

Adenosine Triphosphate↗
PubMed1998

AIDS-related bronchogenic carcinoma: fact or fiction?

OBJECTIVE: Case reviews and retrospective analyses have raised the possibility of an increased frequency of primary lung carcinoma in HIV- and AIDS-infected patients. Conclusions have often been controversial and conflicting. We conducted a population-based epidemiologic study to assess the incidence of lung neoplasms in an HIV/AIDS cohort. MATERIALS AND METHODS: The Texas Department of Health generated descriptive data on lung neoplasms in HIV-AIDS patients whose conditions were diagnosed between 1990 and 1995. The cancer registry matched against all patients whose conditions were diagnosed during the same time interval. Relative risk was measured through standardized incidence ratios of lung neoplasms in the HIV-AIDS population as compared with that of the US population. RESULTS: The HIV-AIDS data file included 26,181 cases. A total of 76 lung cancer cases were identified, of which 36 (47.4%) were primary lung cancers. All major histologies were represented. The observed (36)/expected (5.6) ratio (standard incidence ratio) for primary lung cancer compared to the US population was 6.5 (4.5 to 8.9, 95% confidence interval). CONCLUSIONS: Our data indicate a 6.5-fold increased incidence of primary lung cancer in HIV- and AIDS-infected patients. We present the results of our study, a review of the work of other investigators, and address a potentially even greater public health problem in the HIV/AIDS population than previously realized.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Characterization of G protein and phospholipase C-coupled agonist binding to the Y1 neuropeptide Y receptor in rat brain: sensitivity to G protein activators and inhibitors and to inhibitors of phospholipase C.

Binding of a Y1-subtype-selective agonist of neuropeptide Y (NPY) receptor, (Leu31,Pro34)human peptide YY (LP-PYY), to particulates from four rat brain areas (parietal cortex area 1, piriform cortex, anterior hypothalamus and hippocampus) showed a distinct response to LP-PYY and PYY, a uniformly low sensitivity to ligands selective for the Y2, Y4 and Y5 NPY receptor subtypes and high sensitivity to a Y1 site-selective antagonist, BIBP-3226. The Y1 binding was sensitive to guanine nucleotide-binding protein (G protein) agonist and antagonist nucleotides, with the rank order of guanosine 5'-O-(thiotriphosphate) (GTP gamma S) > GTP > GDP > guanosine 5'-O-(thiodiphosphate). However, guanine nucleotides did not affect about one third of the specific Y1 binding. Most of Y1 binding could be inhibited by a G protein nucleotide site/docking site receptor mimic, mastoparan analog MAS-7. In all areas examined, the Y1 binding of LP-PYY was little affected by up to 100 microM of the antagonists of K+, Na+ and Ca++ channels, protein kinase C, phospholipase A2, phospholipase D and phosphatidylinositol 3-kinase, phospholipase substrate phospholipids, steroids or detergents. However, the binding was potently inhibited by phospholipase C inhibitors (especially the aminosteroid U-73122), which also dissociated the bound Y1 ligand in steady-state conditions. U-73122 also displaced the Y1 binding insensitive to GTP gamma S. Ligand association with the brain Y1 NPY receptor thus strongly depends on activity of both G proteins and phospholipase C, implying specific interactions of these transducers/effectors with the receptor molecule in ligand binding. A portion of brain Y1 sites could be directly coupled to phospholipase(s) C.

Animals↗
PubMed1997

The Hermansky-Pudlak syndrome.

Hermansky-Pudlak Syndrome (HPS) is a rare, inheritable disorder characterized by the classic triad of oculo-cutaneous albinism, platelet dysfunction, and ceroid deposition. An associated complication is pulmonary fibrosis with progressive restrictive lung disease. This report discusses the lung involvement often seen in this condition correlated with radiography, computed tomography, high-resolution computed tomography, and the underlying pathology, by means of two such afflicted siblings. The elder died of respiratory failure while awaiting lung transplantation. The younger sibling is currently undergoing evaluation for transplantation.

Adult↗