title: Relationship between human evolution and neurally mediated syncope disclosed by the polymorphic sites of the adrenergic receptor gene α2B-AR.
abstract: The objective of this study was to clarify the effects of disease on neurally mediated syncope (NMS) during an acute stress reaction. We analyzed the mechanism of the molecular interaction and the polymorphisms of the alpha-2 adrenoreceptor (α2B-AR) gene as the potential psychiatric cause of incentive stress. We focused on the following three genotypes of the repeat polymorphism site at Glu 301-303 in the α2B-AR gene: Glu12/12, Glu12/9, and Glu9/9. On the basis of our clinical research, NMS is likely to occur in people with the Glu12/9 heterotype. To verify this, we assessed this relationship with the interaction of Gi protein and adenylate cyclase by in silico analysis of the Glu12/9 heterotype. By measuring the difference in the dissociation time of the Gi-α subunit twice, we found that the Glu12/9 heterotype suppressed the action of adenylate cyclase longer than the Glu homotypes. As this difference in the Glu repeat number effect is thought to be one of the causes of NMS, we investigated the evolutionary significance of the Glu repeat number. Glu8 was originally repeated in simians, while the Glu12 repeats occurred over time during the evolution of bipedalism in humans. Taken with the Glu12 numbers, NMS would likely become a defensive measure to prevent significant blood flow to the human brain.
authors: Department of Clinical Pharmacology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors: Tomoyoshi
authors: T
authors: Komiyama
authors: The National Institute of Advanced Industrial Science and Technology (AIST), Tokyo Waterfront Bio-IT Research Building 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
authors: Takatsugu
authors: T
authors: Hirokawa
authors: Tokyo Women's Medical University Medical Center East, 2-1-10 Higashiogu, Arakawa-ku, Tokyo, 116-8567, Japan.
authors: Kyoko
authors: K
authors: Sato
authors: The Institute of Medical Science, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors: Akira
authors: A
authors: Oka
authors: Support Center for Medical Research and Education, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors: Hiroshi
authors: H
authors: Kamiguchi
authors: Department of Neurology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors: Eiichiro
authors: E
authors: Nagata
authors: Tokyo Women's Medical University Medical Center East, 2-1-10 Higashiogu, Arakawa-ku, Tokyo, 116-8567, Japan.
authors: Hiroshi
authors: H
authors: Sakura
authors: Tokyo Women's Medical University Medical Center East, 2-1-10 Higashiogu, Arakawa-ku, Tokyo, 116-8567, Japan.
authors: Kuniaki
authors: K
authors: Otsuka
authors: Department of Clinical Pharmacology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors: Hiroyuki
authors: H
authors: Kobayashi
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D004272:DNA, Mitochondrial / Q000032:analysis / Q000145:classification; D004837:Epinephrine / Q000097:blood; D019143:Evolution, Molecular; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011323:Primates / Q000235:genetics; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019462:Syncope, Vasovagal / Q000378:metabolism / Q000473:pathology*; D013816:Thermodynamics
chemical_list: D004272:DNA, Mitochondrial; D018341:Receptors, Adrenergic, alpha-2; D004247:DNA; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D009638:Norepinephrine; D004837:Epinephrine