title: Neuregulin 1 as an endogenous regulator of nicotinic acetylcholine receptors in adult major pelvic ganglion neurons.
abstract: We investigated whether endogenous neuregulin 1 (NRG1) is released in a soluble form (called sNRG1) and upregulates expression of nicotinic acetylcholine receptor (nAChR) in autonomic major pelvic ganglion (MPG) neurons of adult rats. To elicit the release of sNRG1, either the hypogastric nerve or the pelvic nerve was electrically stimulated. Then, the MPG-conditioned medium (CM) was subjected to western blotting using an antibody directed against the N-terminal ectodomain of NRG1. Both sympathetic and parasympathetic nerve activation elicited the release of sNRG1 from MPG neurons in a frequency-dependent manner. The sNRG1 release was also induced by treatment of MPG neurons with either high KCl or neurotrophic factors. The biological activity of the released sNRG1 was detected by tyrosine phosphorylation (p185) of the ErbB2 receptors in MPG neurons. When MPG neurons were incubated for 6 h in the CM, the protein level of the nAChR α3 subunit and ACh-induced current (IACh) density were significantly increased. The CM-induced changes in IACh was abolished by a selective ErbB2 tyrosine kinase inhibitor. Taken together, these data suggest that NRG1 functions as an endogenous regulator of nAChR expression in adult MPG neurons.
authors.affiliation: Department of Physiology, The Brain Research Group, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Han-Gyu
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Cho
authors.affiliation: Department of Physiology, The Brain Research Group, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Choong-Ku
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Department of Physiology, The Brain Research Group, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address: swjeong@yonsei.ac.kr.
authors.forename: Seong-Woo
authors.initials: SW
authors.lastname: Jeong
mesh_terms: D000368:Aged; D000818:Animals; D004558:Electric Stimulation; D045888:Ganglion Cysts / Q000503:physiopathology*; D006801:Humans; D008297:Male; D020890:Neuregulin-1 / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010388:Pelvis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*
chemical_list: D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D011978:Receptors, Nicotinic
keywords: Autonomic; Major pelvic ganglion; Neuregulin 1; Neurotrophic factor; Nicotinic acetylcholine receptor; Pelvic nerve