title: Lack of type VI adenylyl cyclase (AC6) leads to abnormal sympathetic tone in neonatal mice.
abstract: Visceral functions are regulated by a basal sympathetic nerve discharge (SND), also known as 'sympathetic tone'. We demonstrate herein that AC6 existed in tyrosine hydroxylase-positive rostral ventrolateral medulla neurons in the brainstem. Adenylyl cyclase (AC) assays showed lower basal and pituitary adenylate cyclase-activating peptide-evoked AC activities in the brainstem of AC6-null mice, indicating that AC6 is a prominent AC isozyme in the brainstem. Furthermore, two independent lines of AC6-null mice exhibited a much higher SND, recorded from splanchnic sympathetic nerves of neonatal brainstem-spinal cord preparations, than wildtype mice. An assay of urine noradrenaline confirmed this observation. Collectively, AC6 plays a critical role in the regulation of sympathetic tone.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chen-Li
authors.initials: CL
authors.lastname: Chien
authors.forename: Meng-Syuan
authors.initials: MS
authors.lastname: Lin
authors.forename: Hsing-Lin
authors.initials: HL
authors.lastname: Lai
authors.forename: Yu-Shuo
authors.initials: YS
authors.lastname: Wu
authors.forename: Ching-Pang
authors.initials: CP
authors.lastname: Chang
authors.forename: Huei-Mei
authors.initials: HM
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Chang
authors.forename: Chun-Kuei
authors.initials: CK
authors.lastname: Su
authors.forename: Yijuang
authors.initials: Y
authors.lastname: Chern
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine / Q000652:urine; D013116:Spinal Cord / Q000378:metabolism*; D013153:Splanchnic Nerves / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6; D009638:Norepinephrine
keywords: AC6; Adenylyl cyclase; Brainstem; Catecholamine; Sympathetic tone; cAMP