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Multiple dopamine receptors-impact of molecular biology
9thMeeting of the ESN
Q15
VASOACTIW
(VIP) STREBS P.Wiik,
-
THE
POLXl?BPTIDE IWlW8TIRAL NEUROI?iMUNE AXIS AND
Norwegian
De f ence
Research
Establishment, Kjeller, Norway Plasma concentration of VIP, the and VIP receptors, leucocyte the monocyte VIP on effect of oxydative burst ex vivo were studied strenuous days of during five physical exercise with food and sleep deficiency. Plasma concentration of VIP was found to increase, and an of upregulation simultaneous leucocyte VIP receptors was found. coincided with an This upregulation increased VIP stimulated production of cellular cyclic AMP, and a more rapid and stronger VIP inhibition of monocyte oxydative burst was found s a during this stress. Furthermore, glucocorticoids were found to induce VIP leucocyte of upregulation receptors in vitro. The results of this study suggest that inhibitory effects of VIP on leucocyte function during conditions with high levels of glucocorticoids, can be potentiated by VIP receptor upregulation. MULTIPLE WPAMINE MOLECULARBIOLOGY
NEUROPEPTIDASES IN THE IMMUNESYSTEM A.J. Turner Departmentof Biochemistry and Molecular Biology,Universityof Leeds,LEEDS. U.K.
RECEPTORS-IMPACT OF
P.G. Strange, Biological Laboratory, The University, Canterbury, Kent, CT2 7NJ, U.K. and biochemical Whereas pharmacological studies identified two dopamine receptors (Dl, D,) studies have biology molecular D,-like identified seven receptors; (Dz(~~, ‘DZchssjr (bar Dar DS) and I&-like D3, D4). We have established clonal cell lines expressing DZCtij,DzoW, and D3 receptors stably and at high These levels j-10' receptors/cell). are being used to cell lines determine the properties of the receptor subtypes and their coupling to G-proteins. Antibodies have been raised against peptides derived from the D, and D, receptor sequences and will identify receptors in Western immunoprecipitation blot and and can localise experiments Some of the receptors on cells. antibodies will also interfere with the coupling of receptors and Gproteins and so may be useful for functional studies.
Variousneuropeptides, includingenkephalins, serve as signallingmoleculesin both the nervousand immunesystems. Terminationof such neuropeptidesignalsis effectedby cell surfacepeptidases(ectoenzymes) of which the prototypeis endopeptidase-24.11 Molecularcloningof ("enkephalinase"). E-24.11has establishedits identityas CALLA or CDlO, the commonacute lymphoblastic leukaemiaantigen. It is highlyexpressed in variouslymphoidmalignancies.The structure, functionand distribution of E-24.11 in the nervousand immunesystemswill bc describedas well as its potentialrole in the hydrolysisof immunoregulatory peptides. Other cell-surface peptidaseshave also been identified as CD antigens. CD13 is expressed on acute myeloid leukaemic cells and is identical with aminopeptidases N. BP-1/6C3 expressed early B-lineage cells is identical with aminopeptidase A and coexpression of the IL-7 receptor and aminopeptidase A on pre-B cells and of IL-7 producing stromal cells may contribute to an intricate regulatory mechanism for cell signalling.
5-HYDROXYTRYPTAMINE SUPERFAMILIES
(5-HT)
RECEPTOR
Daniel Hoyer SAND02 Pharma Ltd, S60/604, CH 4002 Basel,Switzedand Like GABA and acetylcholine, 5-HT acts via two receptor superfamilies; one group belongs to the G-protein coupled receptor family with seven putative transmembrane spanning regions (5-HT,, 5-HT, and 5-HT,), the other to the ligand gated ion channel receptors @HT,) which are formed of several subunits. 5HT,,, 5-HT,rr, 5-HT,, and 5-HT, receptors appear to modulate preferentiaffy adenylate cyclase activity, U-lT,, and 5-HT, receptors modulate the phosphoifpase C/protein kinase C pathway, and 5-HT, receptors act as fast ion channels, although alternate second messenger systems may exist for a tingle receptor. The diiributions and function of the known receptor subtypes have been studied extensively in the brain and are unique. Some ‘orphan’ receptors, due to the lack of selective ligands (i.e. in the 5HT, family) remain to be subclassified. All receptor subtypes which have been character&d either in binding and/or functional studies (except 5-HT,), have been cfoned. Species differences are puzzling; i.e. 5-tiT,$5-HT,, whiih were believed to represent species variants in rodents and nonrodents, respectively, may in fact coexist in the same species. Numerous subtypes of 5HT, receptors which show clearcut interspecies variations may also exist. These aspects will be discussed in view of recent findings in receptor cloning which largely confirm 5-HT receptor heterogeneity.
Q15
VASOACTIW
(VIP) STREBS P.Wiik,
-
THE
POLXl?BPTIDE IWlW8TIRAL NEUROI?iMUNE AXIS AND
Norwegian
De f ence
Research
Establishment, Kjeller, Norway Plasma concentration of VIP, the and VIP receptors, leucocyte the monocyte VIP on effect of oxydative burst ex vivo were studied strenuous days of during five physical exercise with food and sleep deficiency. Plasma concentration of VIP was found to increase, and an of upregulation simultaneous leucocyte VIP receptors was found. coincided with an This upregulation increased VIP stimulated production of cellular cyclic AMP, and a more rapid and stronger VIP inhibition of monocyte oxydative burst was found s a during this stress. Furthermore, glucocorticoids were found to induce VIP leucocyte of upregulation receptors in vitro. The results of this study suggest that inhibitory effects of VIP on leucocyte function during conditions with high levels of glucocorticoids, can be potentiated by VIP receptor upregulation. MULTIPLE WPAMINE MOLECULARBIOLOGY
NEUROPEPTIDASES IN THE IMMUNESYSTEM A.J. Turner Departmentof Biochemistry and Molecular Biology,Universityof Leeds,LEEDS. U.K.
RECEPTORS-IMPACT OF
P.G. Strange, Biological Laboratory, The University, Canterbury, Kent, CT2 7NJ, U.K. and biochemical Whereas pharmacological studies identified two dopamine receptors (Dl, D,) studies have biology molecular D,-like identified seven receptors; (Dz(~~, ‘DZchssjr (bar Dar DS) and I&-like D3, D4). We have established clonal cell lines expressing DZCtij,DzoW, and D3 receptors stably and at high These levels j-10' receptors/cell). are being used to cell lines determine the properties of the receptor subtypes and their coupling to G-proteins. Antibodies have been raised against peptides derived from the D, and D, receptor sequences and will identify receptors in Western immunoprecipitation blot and and can localise experiments Some of the receptors on cells. antibodies will also interfere with the coupling of receptors and Gproteins and so may be useful for functional studies.
Variousneuropeptides, includingenkephalins, serve as signallingmoleculesin both the nervousand immunesystems. Terminationof such neuropeptidesignalsis effectedby cell surfacepeptidases(ectoenzymes) of which the prototypeis endopeptidase-24.11 Molecularcloningof ("enkephalinase"). E-24.11has establishedits identityas CALLA or CDlO, the commonacute lymphoblastic leukaemiaantigen. It is highlyexpressed in variouslymphoidmalignancies.The structure, functionand distribution of E-24.11 in the nervousand immunesystemswill bc describedas well as its potentialrole in the hydrolysisof immunoregulatory peptides. Other cell-surface peptidaseshave also been identified as CD antigens. CD13 is expressed on acute myeloid leukaemic cells and is identical with aminopeptidases N. BP-1/6C3 expressed early B-lineage cells is identical with aminopeptidase A and coexpression of the IL-7 receptor and aminopeptidase A on pre-B cells and of IL-7 producing stromal cells may contribute to an intricate regulatory mechanism for cell signalling.
5-HYDROXYTRYPTAMINE SUPERFAMILIES
(5-HT)
RECEPTOR
Daniel Hoyer SAND02 Pharma Ltd, S60/604, CH 4002 Basel,Switzedand Like GABA and acetylcholine, 5-HT acts via two receptor superfamilies; one group belongs to the G-protein coupled receptor family with seven putative transmembrane spanning regions (5-HT,, 5-HT, and 5-HT,), the other to the ligand gated ion channel receptors @HT,) which are formed of several subunits. 5HT,,, 5-HT,rr, 5-HT,, and 5-HT, receptors appear to modulate preferentiaffy adenylate cyclase activity, U-lT,, and 5-HT, receptors modulate the phosphoifpase C/protein kinase C pathway, and 5-HT, receptors act as fast ion channels, although alternate second messenger systems may exist for a tingle receptor. The diiributions and function of the known receptor subtypes have been studied extensively in the brain and are unique. Some ‘orphan’ receptors, due to the lack of selective ligands (i.e. in the 5HT, family) remain to be subclassified. All receptor subtypes which have been character&d either in binding and/or functional studies (except 5-HT,), have been cfoned. Species differences are puzzling; i.e. 5-tiT,$5-HT,, whiih were believed to represent species variants in rodents and nonrodents, respectively, may in fact coexist in the same species. Numerous subtypes of 5HT, receptors which show clearcut interspecies variations may also exist. These aspects will be discussed in view of recent findings in receptor cloning which largely confirm 5-HT receptor heterogeneity.