title: Role of L-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine.
abstract: L-carnosine (β-alanyl-L-histidine; CAR) is synthesized in mammalian skeletal muscle. Although the physiological roles of CAR have not yet been clarified, there is evidence that the release of CAR from skeletal muscle during physical exercise affects autonomic neurotransmission and physiological functions. In particular, CAR affects the activity of sympathetic and parasympathetic nerves innervating the adrenal glands, liver, kidney, pancreas, stomach, and white and brown adipose tissues, thereby causing changes in blood pressure, blood glucose, appetite, lipolysis, and thermogenesis. CAR-mediated changes in neurotransmission and physiological functions were eliminated by histamine H1 or H3 receptor antagonists (diphenhydramine or thioperamide) and bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock. Moreover, a carnosine-degrading enzyme (carnosinase 2) was shown to be localized to histamine neurons in the hypothalamic tuberomammillary nucleus (TMN). Thus, CAR released from skeletal muscle during exercise may be transported into TMN-histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of CAR on neurotransmission and physiological function. Thus, CAR appears to influence hypoglycemic, hypotensive, and lipolytic activity through regulation of autonomic nerves and with the involvement of the SCN and histamine. These findings are reviewed and discussed in the context of other recent reports, including those on carnosine synthetases, carnosinases, and carnosine transport.
authors.affiliation: ANBAS Corporation, 4-12-17 Toyosaki, Kita-Ku, Osaka, 531-0072, Japan. knagai@anbas.co.jp
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nagai
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanida
authors.forename: Akira
authors.initials: A
authors.lastname: Niijima
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tsuruoka
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kiso
authors.forename: Yuko
authors.initials: Y
authors.lastname: Horii
authors.forename: Jiao
authors.initials: J
authors.lastname: Shen
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Okumura
mesh_terms: D000818:Animals; D017776:Autonomic Pathways / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D002336:Carnosine / Q000378:metabolism*; D057906:Circadian Clocks / Q000502:physiology*; D004150:Dipeptidases / Q000378:metabolism; D004155:Diphenhydramine / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000494:pharmacology; D008066:Lipolysis; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D013493:Suprachiasmatic Nucleus / Q000293:injuries / Q000473:pathology; D022722:Thermogenesis
chemical_list: D001786:Blood Glucose; D006634:Histamine H1 Antagonists; D054828:Histamine H3 Antagonists; D010880:Piperidines; D006632:Histamine; D004155:Diphenhydramine; D002336:Carnosine; D004150:Dipeptidases; C019673:aminoacyl-histidine dipeptidase; C052075:thioperamide