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A G Blomqvist

Publications and source records attributed to A G Blomqvist.

16 recordsLinked to original sources
PubMed1997

Y-receptor subtypes--how many more?

The Y-receptors belong to the G protein-coupled receptor superfamily and mediate a wide variety of physiological effects, such as regulation of blood pressure, anxiety, memory retention, hormone release and food intake. Since the first human Y-receptor was cloned in 1992, the search for additional subtypes has been an area of intense study. Recently four new NPY-receptor subtypes have been isolated, revealing surprisingly limited sequence identity with values as low as 30%. Several reports indicate further heterogeneity of this receptor family, for example a peripheral Y2 receptor. However, since many studies have been carried out with different peptide analogs and radioligands in different species, there is substantial confusion regarding the pharmacological profile of the receptors. This may have led to an exaggeration of the potential number of discrete receptors.

Amino Acid Sequence↗
PubMed1997

Is health care really a luxury?

Much of the work which has led to a widely held view that the income elasticity of health care spending exceeds one has been based on international cross-section data, or on pooled cross-sections and time series. In this paper we re-examine this view in the context of long-run equilibrium relationships between non-stationary time series, possibly including autonomous trends. Our results cast doubt upon the usefulness of pooling and upon the notion of an elasticity above one.

Canada↗
PubMed1996

Cationic lipid-mediated delivery and expression of prepro-neuropeptide Y cDNA after intraventricular administration in rat: feasibility and limitations.

The utility of in vivo lipofection for delivery and expression of a neuropeptide gene in the adult rat brain was explored. Prepro-neuropeptide Y (NPY) cDNA was cloned into the episomal eucaryotic expression vector pCEP4. This construct was complexed to lipofectamine or lipofectin. Complexed DNA was injected into the lateral ventricles of adult rats. Brains were removed for analysis following various time intervals. Polymerase chain reaction (PCR) reactions were designed for specific detection of endogenous and vector derived NPY sequence, respectively. PCR of DNA preparations from 5 major brain regions (frontal and parietal cortex, striatum, hypothalamus, brain stem) demonstrated presence of vector DNA up to 1 month (longest interval studied) in all brain regions. Reverse-transcription (RT-) PCR of DNase treated RNA-preparations from brain tissue demonstrated presence of both vector-derived and endogenous NPY mRNA in treated animals, while only endogenous mRNA was detected in controls. In situ hybridization histochemistry indicated scattered patches of vector uptake into tissue in the vicinity of the CSF compartment, but not into deeper located structures. Weight gain was not affected, indicating that the expression levels achieved may not be sufficient to play a functional role, and/or may need to be targeted to specific brain areas. These findings suggest a potential for cationic lipid mediated gene transfer in the brain as an experimental tool and as a possible future therapeutic principle, but also indicate the need for optimization of delivery strategies in order to achieve functionally relevant expression levels.

Animals↗
PubMed1995

Cloning of a human receptor of the NPY receptor family with high affinity for pancreatic polypeptide and peptide YY.

Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are structurally related peptides found in all higher vertebrates. NPY is expressed exclusively in neurons, whereas PYY and PP are produced primarily in gut endocrine cells. Several receptor subtypes have been identified pharmacologically, but only the NPY/PYY receptor of subtype Y1 has been cloned. This is a heptahelix receptor that couples to G proteins. We utilized Y1 sequence information from several species to clone a novel human receptor with 43% amino acid sequence identity to human Y1 and 53% identity in the transmembrane regions. The novel receptor displays a pharmacological profile that distinguishes it from all previously described NPY family receptors. It binds PP with an affinity (Ki) of 13.8 pM, PYY with 1.44 nM, and NPY with 9.9 nM. Because these data may identify the receptor as primarily a PP receptor, we have named it PP1. In stably transfected Chinese hamster ovary cells the PP1 receptor inhibits forskolin-stimulated cAMP synthesis. Northern hybridization detected mRNA in colon, small intestine, pancreas, and prostate. As all three peptides are present in the gut through either endocrine release or innervation, all three peptides may be physiological ligands to the novel NPY family receptor PP1.

Amino Acid Sequence↗
PubMed1995

Cloning and sequence analysis of a neuropeptide Y/peptide YY receptor Y1 cDNA from Xenopus laevis.

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides that share at least two distinct receptors denoted Y1 and Y2. The Y1 receptor has previously been cloned in man, rat and mouse. We describe here the cloning and sequence of a Xenopus laevis Y1 receptor that shares 81% amino acid sequence identity with the human receptor in the region spanning transmembrane (TM) regions I to VII. The extracellular amino-terminal part, TM IV and the second extracellular loop contain several replacements suggesting that these portions have no or limited direct interactions with the peptide ligands. The intracellular regions including the carboxy-terminal tail are nearly identical between Xenopus and mammals, suggesting strong structural constraints on the portions that may interact with G proteins.

Amino Acid Sequence↗
PubMed1994

Neuropeptide-Y gene expression in the goldfish brain: distribution and regulation by ovarian steroids.

Neuropeptide-Y (NPY) has been recently cloned from a goldfish cDNA library. Using a probe derived from this cDNA clone, the distribution and regulation of NPY mRNA in the goldfish brain were examined in the present study by in situ hybridization, Northern blot analysis, and ribonuclease protection assay. Frozen tissue sections from the goldfish brain and pituitary were hybridized with a digoxigenin-labeled RNA probe. Hybridization signal was detected mainly in fore-brain regions, particularly in the nucleus entopeduncularis of the ventral telencephalon, the preoptic area (POA), the olfactory bulbs, and various thalamic regions. In the midbrain, NPY mRNA was found in the optic-tectum and locus coeruleus. Northern blot hybridization of total RNA extracted from different brain areas with a 32P-labeled RNA probe detected a single mRNA species and confirmed that most NPY mRNA was present in telencephalon/POA and optic-tectum/thalamus. Our previous physiological studies showed that the ovarian steroids testosterone (T) and estradiol (E2) have potentiating effects on the actions of NPY on gonadotropin and GH release. Therefore, we also tested the possibility that T and E2 may modulate NPY gene expression. Fish were implanted ip with pellets containing T, E2, or no steroid (control) for 5 days, RNA was extracted, and NPY mRNA levels were estimated using a ribonuclease protection assay. Pretreatment with T or E2 induced a 2- to 3-fold increase in NPY mRNA levels in the telencephalon/POA, but not in the optic-tectum/thalamus. In situ hybridization using brains taken from T-implanted fish demonstrated that the site of steroid action is the POA. This report represents the first study on NPY gene expression in a nonmammalian species and demonstrates that 1) NPY mRNA is present in the neuroendocrine regulatory centers; and 2) ovarian steroids stimulate NPY gene expression in the POA.

Animals↗
PubMed1993

Evolutionary conservation of synaptosome-associated protein 25 kDa (SNAP-25) shown by Drosophila and Torpedo cDNA clones.

The neuron-specific proteins SNAP-25 (synaptosome-associated protein 25 kDa), synaptobrevin and syntaxin, are localized to presynaptic terminals in mammals and have been found to associate with proteins involved in vesicle docking and membrane fusion. We describe here SNAP-25 cDNA clones from the fruit fly Drosophila melanogaster and the ray Torpedo marmorata. In situ hybridization showed that SNAP-25 mRNA is exclusively found in brain and ganglia in Drosophila with a pattern suggesting expression in most neurons. The Drosophila and Torpedo proteins show 61 and 81% amino acid identity to mouse SNAP-25, a degree of conservation similar to that previously reported for synaptobrevin. None of the SNAP-25 sequences has a membrane-spanning region, but all contain a cluster of cysteine residues that can be palmitoylated for membrane attachment. SNAP-25 displays sequence similarity to syntaxin A and B. These data show that SNAP-25 and synaptobrevin, which are both implicated in vesicle docking and/or membrane fusion, have both been highly conserved during evolution. This supports the existence of a basic molecular machinery for synaptic vesicle docking in vertebrate and invertebrate synapses.

Amino Acid Sequence↗
PubMed1993

A proposed bovine neuropeptide Y (NPY) receptor cDNA clone, or its human homologue, confers neither NPY binding sites nor NPY responsiveness on transfected cells.

Receptors with seven transmembrane domains (7TM) constitute a large family of structurally and functionally related proteins which respond to various types of ligands. We describe here the cloning and expression of a human 7TM receptor, denoted hFB22 (human Fetal Brain 22), which is the homologue (92% amino acid identity) of a bovine receptor (LCR1) reported by others to bind neuropeptide Y (NPY) with a pharmacological profile of the Y3 receptor subtype. However, upon expression in COS1 (confirmed by Northern analysis), COS7 or CHO-K1 cells, the hFB22 receptor did not confer specific 125I-Bolton-Hunter-NPY, 3H-propionyl-NPY or 125I-peptide YY (PYY) binding sites, in either intact cells or in membrane preparations. Similarly, cells transfected with the corresponding bovine clone (LCR1) did not show specific NPY/PYY binding exceeding that resulting from endogenous binding sites; mock-transfected COS7 cells, used frequently for heterologous expression of receptors, were found to have endogenous specific 125I-NPY binding sites (Bmax = 112 fmol/mg protein; Kd = 0.25 nM). Moreover, the hFB22 transfected cells, when compared to control transfected cells, did not display de novo NPY- or PYY-induced second messenger responses, i.e., (1) inhibition of forskolin-stimulated cAMP accumulation or (2) 45Ca2+ influx. The presence of hFB22 mRNA was detected in several human neuroblastoma cell lines, none of which was found to express Y3-like NPY binding sites. hFB22 displays 39% amino acid sequence identity (in the transmembrane regions) to the human interleukin-8 receptor, and 32-36% amino acid identity to the human receptors of angiotensin II, bradykinin, and n-formylpeptide, but only 23% amino acid identity to the previously described human NPY/PYY receptor of the Y1 receptor subtype. Our results show that hFB22 and LCR1 do not encode NPY receptors, and their true ligand(s) remains to be identified.

Amino Acid Sequence↗
PubMed1993

Actions of goldfish neuropeptide Y on the secretion of growth hormone and gonadotropin-II in female goldfish.

Neuropeptide Y (NPY) has been recently characterized in the goldfish and the sequence deduced from goldfish brain cDNA clones reveals that goldfish NPY (gNPY) has over 86% identity with human NPY (hNPY) (Blomqvist et al., 1992, Proc. Natl. Acad. Sci. USA 89, 2350-2354). In the present study, we used synthetic gNPY to investigate the role of NPY in the regulation of growth hormone (GH) and gonadotropin-II (GtH-II) in the goldfish. The dose-response relationships of gNPY on GH and GtH-II release were first tested using an in vitro perifusion system for pituitary fragments. It was found that gNPY stimulated both GH and GtH-II release in a dose-dependent manner, with ED50 values of 1.89 +/- 0.9 nM for GH and 4.19 +/- 2.9 nM for GtH-II. In addition, the C-terminal fragment gNPY (18-36) stimulated the release of both GH and GtH-II, but with lower potency than did the intact molecule. These results confirm our previous findings using hNPY. The interactions of gNPY and other GH and GtH-II regulators were also examined in the present studies. Prolonged infusion of sGnRH induced initial peak releases of GH and GtH-II, followed by a second phase of sustained hormone release at a reduced level. Application of a 5-min pulse of gNPY during the second phase of sGnRH action further stimulated GH and GtH-II release, but only to the levels similar to those induced by gNPY alone. Prolonged infusion with gNPY induced a rapid desensitization of GH and GtH-II release; the hormone levels returned to basal within 25 min in the continued presence of gNPY. Administration of 5-min pulse of sGnRH during the desensitization phase of continuous gNPY perfusion induced a similar GH response to that induced by sGnRH alone, whereas the GtH-II responses to sGnRH given during gNPY infusion were smaller than the responses to sGnRH alone, suggesting that the mechanisms of gNPY stimulation on GH and GtH-II release may be somewhat different. The gNPY-induced GH release was blocked by somatostatin, a known GH inhibitor; the gNPY-induced GtH-II release was reduced by dopamine, a known inhibitor for GtH-II. Finally, intraperitoneal injection of gNPY induced time- and dose-dependent increases in serum GH and GtH-II levels. Together, these results suggest that NPY may play a physiological role in the regulation of GH and GtH-II secretion in the goldfish.

Animals↗
PubMed1993

Evolution of neuropeptide Y and its related peptides.

1. The neuropeptide Y (NPY) family of peptides includes also the gut endocrine peptide YY (PYY), tetrapod pancreatic polypeptide (PP), and fish pancreatic peptide-tyrosine (PY). All peptides are 36 amino acids long. 2. Sequences from many types of vertebrates show that NPY has remained extremely well conserved throughout vertebrate evolution with 92% identity between mammals and cartilaginous fishes. 3. PYY has 97-100% identity between cartilaginous fishes and bony fishes, but is less conserved in amphibians and mammals (83% identity between amphibians and sharks and 75% identity between mammals and sharks). 4. NPY and PYY share 70-80% identity in most species. 5. Both NPY and PYY were present in the early vertebrate ancestor because both peptides have been found in lampreys. 6. The tissue distribution appears to have been largely conserved between phyla, except that PYY has more widespread neuronal expression in lower vertebrates. 7. Pancreatic polypeptide has diverged considerably among tetrapods leaving only 50% identity between mammals, birds/reptiles and frogs. 8. Several lines of evidence suggest that the PP gene arose by duplication of the PYY gene, probably in the early evolution of the tetrapods. 9. The pancreatic peptide PY found in anglerfish and daddy sculpin may have resulted from an independent duplication of the PYY gene. 10. The relationships of the recently described mollusc and worm peptides NPF and PYF with the NPY family still appear unclear.

Amino Acid Sequence↗
PubMed1993

The receptor revolution--multiplicity of G-protein-coupled receptors.

The superfamily of G-protein-coupled receptors (GPCR) is probably the largest protein-encoding gene family in our genome. It is already known to include hundreds of members and many more are expected to emerge as the molecular cloning revolution proceeds. By definition the GPCR respond to ligands by interacting with intracellular G-proteins and thereby transduce external signals to the interior of the cell. A large body of evidence suggests that the GPCR are organized in the cell membrane like bacteriorhodopsin (BR). All GPCR possess seven hydrophobic membrane-spanning segments which seem to form a characteristic BR-like barrel structure. Thus, the three-dimensional structure of BR may be used as a framework for computer-aided structural modelling of GPCR. The ligands which activate the various members of the GPCR family include an enormous variety of molecules such as amines, amino acids and peptides as well as several small hydrophobic molecules. Many ligands bind to multiple distinct GPCR, e.g. neuropeptide Y (NPY). We have isolated molecular clones encoding a human NPY receptor whose binding properties conform to those of the Y1 subtype. This clone will be a useful tool in our efforts to unravel the molecular mechanisms of the many physiological functions of neuropeptide Y.

Amino Acid Sequence↗
PubMed1992

Cloning and functional expression of a human neuropeptide Y/peptide YY receptor of the Y1 type.

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides that primarily function as neurotransmitter and gastrointestinal hormone, respectively. Previous functional and binding data have indicated the existence of at least three distinct receptor types, Y1, Y2, and Y3, for NPY and/or PYY in mammals. We describe here a human Y1 cDNA clone, hY1-5, isolated from a fetal brain library. The human Y1 receptor consists of 384 amino acids and has seven putative transmembrane domains like other members of the G-protein-coupled superfamily of receptors. In the region spanning the transmembrane domains, the Y1 receptor displays 29% sequence identity to human tachykinin receptors, but it only shows 21% and 23% homology with proposed bovine (LCR1) and Drosophila (PR4) NPY receptor clones, respectively. Northern blot analysis of a human neuroblastoma cell line, SK-N-MC, previously used by many investigators as a model system for studies on the Y1 receptor, revealed a single 3.5-kilobase mRNA species. Reverse transcriptase-polymerase chain reaction analysis indicated expression also in human cultured vascular smooth muscle cells, supporting the view that the Y1 receptor is associated with NPY/PYY-evoked vasoconstriction. When expressed in COS1 cells, hY1-5 conferred specific 125I-PYY binding sites with displacement patterns characteristic of the Y1 receptor, i.e. PYY greater than or equal to NPY greater than or equal to [Leu31,Pro34]NPY much greater than NPY2-36 greater than C2NPY greater than pancreatic polypeptide greater than NPY13-36 greater than NPY18-36. Moreover, in the Y1 receptor-transfected COS1 cells, but not in type 1 angiotensin II receptor-transfected control cells, NPY and PYY accelerated 45Ca2+ influx and inhibited forskolin-stimulated cAMP accumulation, both phenomena being characteristic of the mammalian Y1 receptor.

Amino Acid Sequence↗
PubMed1992

Strong evolutionary conservation of neuropeptide Y: sequences of chicken, goldfish, and Torpedo marmorata DNA clones.

Neuropeptide Y (NPY) is an abundant and widespread neuropeptide in the nervous system of mammals. NPY belongs to a family of 36-amino acid peptides that also includes pancreatic polypeptide and the endocrine gut peptide YY as well as the fish pancreatic peptide Y. To study the evolution of this peptide family, we have isolated clones encoding NPY from central nervous system cDNA libraries of chicken, goldfish, and the ray Torpedo marmorata, as well as from a chicken genomic library. The predicted chicken NPY amino acid sequence differs from that of rat at only one position. The goldfish sequence differs at five positions and shows that bony fishes have a true NPY peptide in addition to their pancreatic peptide Y. The Torpedo sequence differs from that of rat at three positions. As Torpedo NPY has no unique positions when compared with the other sequences, it seems to be identical to the NPY of the common ancestor of cartilaginous fishes, bony fishes, and tetrapods after 420 million years of evolution. The 30-amino acid carboxyl-terminal extension of the NPY precursor also displays considerable sequence conservation. These results show that NPY is one of the most highly conserved neuroendocrine peptides.

Amino Acid Sequence↗
PubMed1992

The Swedish health care system--an economist's view.

This article compares the organization of the Swedish health care system with that in three other countries, the U.S., the U.K., and Canada, focussing on three main areas: (1) the provision and financing (public or private) of health insurance, including the question of the quality of the insurance protection offered; (2) the organization of the production of health services, and the economic incentives on the system's decision-makers (doctors, hospital managers, politicians, etc.). Possible answers are suggested to the question why one country (the U.K.) is able to provide health care to its population at an average cost considerably below that of the others: Differences in the quality of the insurance protection and health services; in the incentives on the system managers to exercise cost control; and in the incentives on service providers such as physicians, to consider cost-effectiveness when making treatment decisions. An attempt is made to suggest lessons for health care reform in Sweden and elsewhere.

Canada↗
PubMedDate not supplied

Unemployment of the educated and emigration of post-secondary graduates from the LDCs.

The author examines the emigration of educated individuals from developing countries and reviews selected approaches to the study of international human capital flows. Attention is then given to two policy issues: the financing of postsecondary education and an international brain drain tax. The following factors are identified as critical in their impact on educated worker migration: "(a) the rigidity or flexibility of the wage in the market for the services of educated labour; (b) the extent of government subsidy (explicit or implicit) of the cost of post-secondary education; (c) the extent of responsiveness of the investment in education to the private return on such investment or its being exogenously controlled by the government; and (d) the type of restrictions (if any) imposed by the receiving industrialized countries on the migration flows from the LDCs." Comments by M. Ali Khan on a previous article by Blomqvist on the subject are also included (pp. 655-6).

Demography↗