title: Gender bias in gastroparesis: is nitric oxide the answer?
abstract: Accumulating evidence suggests that gender-related differences are prominent in gastric motility functions in both health and disease. Women are more susceptible to gastroparesis than men. Though the mechanism(s) involved are not fully understood, impairment of the nitrergic system is one of the main factors responsible for the disease. Uncoupling of neuronal nitric oxide synthase (nNOS) causes a decreased synthesis of NO leading to a reduction in smooth muscle relaxation. Tetrahydrobiopterin (BH(4)) (an essential cofactor for nNOS) is a key regulator of nNOS activity for stomach dysfunction and gastroparesis. In addition, BH(4) has been shown to be a potent antioxidant and anti-inflammatory agent. Well established by results from our laboratory, a diminished intracellular (BH(4):total biopterin) ratio in diabetic female rats significantly impairs nNOS activity and function. Recent research has been focused on BH(4) biosynthesis and gastroparesis because reduced BH(4) cofactor levels can alter the production of NO by nNOS. Researchers are now paying more attention to the possibility of using BH(4) as a therapeutic strategy in gastroparesis. The purpose of this review is to provide an overview of the regulation and function of nNOS by sex hormones and BH(4) and its potential role in the treatment of gastroparesis.
authors.affiliation: Department of Physiology, Center for Women's Health Research, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Blvd, Nashville, TN 37208, USA. pgangula@mmc.edu
authors.forename: P R R
authors.initials: PR
authors.lastname: Gangula
authors.forename: K R
authors.initials: KR
authors.lastname: Sekhar
authors.forename: S
authors.initials: S
authors.lastname: Mukhopadhyay
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000502:physiology / Q000627:therapeutic use; D005260:Female; D018589:Gastroparesis / Q000188:drug therapy / Q000503:physiopathology*; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D012739:Gonadal Steroid Hormones; D001708:Biopterins; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; C003402:sapropterin