Nicotinic receptor gene cluster on rat chromosome 8 in nociceptive and blood pressure hyperresponsiveness

Khan, Imran; Singletary, Erin; Alemayehu, Adamu; Stanislaus, Shanaka; Printz, Morton P.; Yaksh, Tony L.; Taylor, Palmer

doi:10.1152/physiolgenomics.00079.2002

Cited by 7 publications

(7 citation statements)

References 35 publications

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“…␣3, ␣5, and ␤4 subunits are encoded by a gene cluster localized to rat chromosome 8. They appear to be candidate genes for the spontaneously hypertensive rats phenotype (Khan et al, 2002). As reported in studies with dorsal root and peripheral ganglia (Keiger and Alker, 2000;Genzen et al, 2001), we identified transcripts for the five nicotinic receptor subunits in DRG neurons.…”

Section: Nicotinic Receptor Binding Sites In Rat Spinal Cordsupporting

confidence: 56%

Nicotinic acetylcholine receptor distribution in relation to spinal neurotransmission pathways

Khan

Osaka

Stanislaus

et al. 2003

J of Comparative Neurology

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Neuronal nicotinic receptors (nAChR) are pentameric assemblies of subunits of a gene family where specified combinations of alpha and beta subunits form functional receptors. To extend our understanding of the role of spinal nAChR in the processing of sensory stimuli and regulation of autonomic and motor responses, we initiated investigations to localize nAChR subunit expression within discrete spinal regions and cell types. High-affinity epibatidine binding was present in the superficial dorsal and ventral horns, the mediolateral and central canal regions. RT-PCR identified transcripts for alpha3, alpha4, alpha5, beta2, and beta4 in both spinal cord parenchyma and dorsal root ganglia (DRG). Our affinity-purified antibodies against alpha3, alpha4, alpha5, beta2, and beta4 subunits identified specific protein bands of appropriate molecular mass (preadsorbed with the respective antigens) in specific tissues and cells that express nicotinic receptors, including the spinal cord and DRG neurons. Having established the absence of crossreactivity with related subunits, specific fluorescence labeling of nerve terminals and cell bodies was achieved and correlated with the distribution of defined marker proteins and nicotinic receptor binding sites determined autoradiographically. Our findings indicate that alpha3, alpha4, alpha5, beta2, and beta4 subunits are all expressed on primary afferents (IB4-positive terminals) in the spinal cord. The predominant presynaptic (synaptophysin colocalization) labeling is in the superficial layer of the dorsal horn. These receptor subunits, except for beta4, are also present in postsynaptic autonomic (anti-bNOS-positive) and somatic motor neurons (anti-VAChT-positive). The alpha3, alpha5, and beta2 subunits showed additional staining in glial (anti-GFAP-positive) cells. These studies reveal a dense and distinguishable distribution of nAChR subunits in the spinal cord and point toward future therapeutic targeting for specific spinal actions.

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Section: Nicotinic Receptor Binding Sites In Rat Spinal Cordsupporting

confidence: 56%

Nicotinic acetylcholine receptor distribution in relation to spinal neurotransmission pathways

Khan

Osaka

Stanislaus

et al. 2003

J of Comparative Neurology

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“…Peripheral and central nervous system control of cardiovascular function mediated through the autonomic nervous system is critical in homeostatic maintenance of blood pressure and responsiveness to exercise, postural alterations, and stress (Suh et al, 1936;Vargas and Brezenoff, 1988;Buccafusco, 1996;Khan et al, 2002). Central cholinergic pathways in the spinal cord and higher brain centers modulate cardiovascular responses to influence basal blood pressure and baroreflex or pressor responses via the neurotransmitter acetylcholine (ACh).…”

Section: Introductionmentioning

confidence: 99%

Naturally Occurring Variations in the Human Cholinesterase Genes: Heritability and Association with Cardiovascular and Metabolic Traits

Valle¹,

Radić²,

Rana³

et al. 2011

J Pharmacol Exp Ther

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Cholinergic neurotransmission in the central and autonomic nervous systems regulates immediate variations in and longerterm maintenance of cardiovascular function with acetylcholinesterase (AChE) activity that is critical to temporal responsiveness. Butyrylcholinesterase (BChE), largely confined to the liver and plasma, subserves metabolic functions. AChE and BChE are found in hematopoietic cells and plasma, enabling one to correlate enzyme levels in whole blood with hereditary traits in twins. Using both twin and unrelated subjects, we found certain single nucleotide polymorphisms (SNPs) in the ACHE gene correlated with catalytic properties and general cardiovascular functions. SNP discovery from ACHE resequencing identified 19 SNPs: 7 coding SNPs (cSNPs), of which 4 are nonsynonymous, and 12 SNPs in untranslated regions, of which 3 are in a conserved sequence of an upstream intron. Both AChE and BChE activity traits in blood were heritable: AChE at 48.8 Ϯ 6.1% and BChE at 81.4 Ϯ 2.8%. Allelic and haplotype variations in the ACHE and BCHE genes were associated with changes in blood AChE and BChE activities. AChE activity was associated with BP status and SBP, whereas BChE activity was associated with features of the metabolic syndrome (especially body weight and BMI). Gene products from cDNAs with nonsynonymous cSNPs were expressed and purified. Protein expression of ACHE nonsynonymous variant D134H (SNP6) is impaired: this variant shows compromised stability and altered rates of organophosphate inhibition and oxime-assisted reactivation. A substantial fraction of the D134H instability could be reversed in the D134H/R136Q mutant. Hence, common genetic variations at ACHE and BCHE loci were associated with changes in corresponding enzymatic activities in blood.

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“…They mapped a quantitative trait locus (QTL) for blood pressure (BP) on rat chromosome 8 (Chr 8). Kren and coworkers established a congenic strain to prove that such as a QTL really existed [2][3][4]. Independently, Takami and collaborators found one locus for the peroxisamol 3-keto acyl-CoA thiolase on Chr 8 cosegregated with BP in crosses involving SHR and Dahl/Iwai salt-sensitive rats [5].…”

Section: Introductionmentioning

confidence: 99%

Dissecting quantitative trait loci into opposite blood pressure effects on Dahl rat chromosome 8 by congenic strains

Ariyarajah

Palijan

Dutil

et al. 2004

Journal of Hypertension

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Nicotinic receptor gene cluster on rat chromosome 8 in nociceptive and blood pressure hyperresponsiveness

Cited by 7 publications

References 35 publications

Nicotinic acetylcholine receptor distribution in relation to spinal neurotransmission pathways

Nicotinic acetylcholine receptor distribution in relation to spinal neurotransmission pathways

Naturally Occurring Variations in the Human Cholinesterase Genes: Heritability and Association with Cardiovascular and Metabolic Traits

Dissecting quantitative trait loci into opposite blood pressure effects on Dahl rat chromosome 8 by congenic strains

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