Biomedical subjects

J Behan

Publications and source records attributed to J Behan.

8 recordsLinked to original sources

PubMed2001

Identification and pharmacological characterization of a novel human melanin-concentrating hormone receptor, mch-r2.

Melanin-concentrating hormone (MCH) is a neuropeptide highly expressed in the brain that regulates several physiological functions mediated by receptors in the G protein-coupled receptor family. Recently an orphan receptor, SLC-1, has been identified as an MCH receptor (MCH-R1). Herein we identify and characterize a novel receptor for human MCH (MCH-R2). The receptor is composed of 340 amino acids encoded by a 1023-base pair cDNA and is 35% homologous to SLC-1. (125)I-MCH specifically bound to Chinese hamster ovary cells stably expressing MCH-R2. MCH stimulated dose-dependent increases in intracellular free Ca(2+) and inositol phosphate production in these cells but did not affect cAMP production. The pharmacological profile for mammalian MCH, [Phe(13),Tyr(19)]MCH, and salmon MCH at MCH-R2 differed compared with MCH-R1 as assessed by intracellular signaling and radioligand binding assays. The EC(50) in signaling assays and the IC(50) in radioligand binding assays of salmon MCH was an order of magnitude higher than mammalian MCH at MCH-R2. By comparison, the EC(50) and IC(50) values of salmon MCH and mammalian MCH at MCH-R1 were relatively similar. Blot hybridization revealed exclusive expression of MCH-R2 mRNA in several distinct brain regions, particularly in the cortical area, suggesting the involvement of MCH-R2 in the central regulation of MCH-mediated functions.

Amino Acid Sequence↗

PubMed2001

Cloning and characterization of a novel human histamine receptor.

Histamine exerts its numerous physiological functions through interaction with G protein-coupled receptors. Three such receptors have been defined at both the pharmacological and molecular level, while pharmacological evidence hints at the existence of further subtypes. We report here the cloning and characterization of a fourth histamine receptor subtype. Initially discovered in an expressed-sequence tag database, the full coding sequence (SP9144) was subsequently identified in chromosome 18 genomic sequence. This virtual coding sequence exhibited highest homology to the H(3) histamine receptor and was used to generate a full-length clone by polymerase chain reaction (PCR). The distribution of mRNA encoding SP9144 was restricted to cells of the immune system as determined by quantitative PCR. HEK-293 cells transiently transfected with SP9144 and a chimeric G protein alpha-subunit (Galpha(q/i1,2)) exhibited increases in intracellular [Ca(2+)] in response to histamine but not other biogenic amines. SP9144-transfected cells exhibited saturable, specific, high-affinity binding of [(3)H]histamine, which was potently inhibited by H(3) receptor-selective compounds. The rank order and potency of these compounds at SP9144 differed from the rank order at the H(3) receptor. Although SP9144 apparently coupled to Galpha(i), HEK-293 cells stably transfected with SP9144 did not exhibit histamine-mediated inhibition of forskolin-stimulated cAMP levels. However, both [(35)S]GTPgammaS binding and phosphorylation of mitogen-activated protein kinase were stimulated by histamine via SP9144 activation. In both of these assays, SP9144 exhibited evidence of constitutive activation. Taken together, these data demonstrate that SP9144 is a unique, fourth histamine receptor subtype.

Amino Acid Sequence↗

PubMed2000

A novel hepatointestinal leukotriene B4 receptor. Cloning and functional characterization.

Leukotriene B(4) (LTB(4)) is a product of eicosanoid metabolism and acts as an extremely potent chemotactic mediator for inflammation. LTB(4) exerts positive effects on the immigration and activation of leukocytes. These effects suggest an involvement of LTB(4) in several diseases: inflammatory bowel disease, psoriasis, arthritis, and asthma. LTB(4) elicits actions through interaction with one or more cell surface receptors that lead to chemotaxis and inflammation. One leukotriene B(4) receptor has been recently identified (LTB(4)-R1). In this report we describe cloning of a cDNA encoding a novel 358-amino acid receptor (LTB(4)-R2) that possesses seven membrane-spanning domains and is homologous (42%) and genetically linked to LTB(4)-R1. Expression of LTB(4)-R2 is broad but highest in liver, intestine, spleen, and kidney. In radioligand binding assays, membranes prepared from COS-7 cells transfected with LTB(4)-R2 cDNA displayed high affinity (K(d) = 0.17 nm) for [(3)H]LTB(4). Radioligand competition assays revealed high affinities of the receptor for LTB(4) and LTB(5), and 20-hydroxy-LTB(4), and intermediate affinities for 15(S)-HETE and 12-oxo-ETE. Three LTB(4) receptor antagonists, 14,15-dehydro-LTB(4), LTB(4)-3-aminopropylamide, and U-75302, had high affinity for LTB(4)-R1 but not for LTB(4)-R2. No apparent affinity binding for the receptors was detected for the CysLT1-selective antagonists montelukast and zafirlukast. LTB(4) functionally mobilized intracellular calcium and inhibited forskolin-stimulated cAMP production in 293 cells. The discovery of this new receptor should aid in further understanding the roles of LTB(4) in pathologies in these tissues and may provide a tool in identification of specific antagonists/agonists for potential therapeutic treatments.

Amino Acid Sequence↗

PubMed2000

Identification of a novel neuromedin U receptor subtype expressed in the central nervous system.

Neuromedin U is a neuropeptide prominently expressed in the upper gastrointestinal tract and central nervous system. Recently, GPR66/FM-3 (NmU-R1) was identified as a specific receptor for neuromedin U. A BLAST search of the GenBank(TM) genomic database using the NmU-R1 cDNA sequence revealed a human genomic fragment encoding a G protein-coupled receptor that we designated NmU-R2 based on its homology to NmU-R1. The full-length NmU-R2 cDNA was subsequently cloned, stably expressed in 293 cells, and shown to mobilize intracellular calcium in response to neuromedin U. This response was dose-dependent (EC(50) = 5 nm) and specific in that other neuromedins did not induce a calcium flux in receptor-transfected cells. Expression analysis of human NmU-R2 demonstrated its mRNA to be most highly expressed in central nervous system tissues. Based on these data, we conclude that NmU-R2 is a novel neuromedin U receptor subtype that is likely to mediate central nervous system-specific neuromedin U effects.

Amino Acid Sequence↗

PubMed1999

The effect of odour priming on long latency visual evoked potentials of matching and mismatching objects.

This study reports a cross-modal, olfactory/visual event related potential (ERP) using odours as olfactory primes. The results show a difference in the ERP waveform for the N400 waveform when a visual image does not match the priming odour. An N400 peak was produced for both the matched and mismatched conditions but the peaks were significantly more negative for the mismatched condition. By the use of non-food odours this study extends an earlier finding by Grigor, who, using the same ERP paradigm, obtained similar results for food odours and photographs of food.

Adult↗

PubMed1999

Visual event related potentials modulated by contextually relevant and irrelevant olfactory primes.

Visual evoked potentials were recorded from 16 scalp locations on 10 young subjects during presentation of a series of high-quality photographs on a computer screen. The photographs consisted of equal numbers of pictures of fruit (citrus and non-citrus fruits), flowers (roses and other flowers) and objects (e.g. buildings, vehicles, animals etc.). Every picture was different in order to avoid repetition effects. The pictures were presented under four odour conditions: no odour, rose odour, jasmine odour and citrus odour. In order to keep the subjects alert they were asked to make categorizing decisions for the visual stimuli (e.g. flower or fruit). No decision was required concerning the relationship between the visual stimulus and the odour. As expected, the N400 peak was more negative when the picture stimulus did not match the odour. It is hypothesized that the N400 peak can be used as a measure of relatedness of a sensory stimulus to a previous or on-going prime, irrespective of the mode of the stimuli.

Adult↗

PubMed1996

Victorian hospital nurses' research attitudes and activity.

Four hundred and fiftyeight registered nurses from seven Victorian hospitals were surveyed to establish their attitudes to nursing research, their levels of research activity and whether working in a hospital with a nursing research policy influenced their attitudes and activities. The results showed that respondents had favourable attitudes to, and considerable interest in, nursing research. They made moderate estimates of their own research skills and had a modest level of research activity, and the data indicated there was potential for this to be increased. Tertiary graduates and Grade 4 and above nurses had more positive attitudes to research and were more likely to have been involved in research, and graduates also had more confidence in their research abilities than non-graduates. The existence of a hospital nursing research policy was not associated with differences in nurses' research attitudes or activities. Major impediments to conducting research were perceived to be workloads and lack of time. Providing time for research appears to be the greatest challenge to improving practice through clinical nursing research.

Adult↗

PubMedDate not supplied

How many hospitals have a nursing research policy? A Victorian survey.

Directors of nursing in 29 Victorian hospitals responded to a questionnaire which sought information on their hospitals' nursing research policies, structures and education and on the level of organisational support for nursing research. One quarter of the hospitals had nursing research policies, 45% expected nurses to be involved in research, 31% had nursing positions with primary research functions, 31% had nursing research committees and 50% provided some research education. Hospitals which had a written policy reported significantly higher levels of administrative support for nursing research and were more likely to have a designated nursing research position. It was concluded that the adoption of a policy on nursing research is associated with organisational support for nursing research in Victorian hospitals.

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