title: Myosin Va plays a role in nitrergic smooth muscle relaxation in gastric fundus and corpora cavernosa of penis.
abstract: The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction.
authors: Divisions of Surgery, VA Boston Healthcare System and Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Arun
authors: A
authors: Chaudhury
authors: Division of Urology, VA Boston Healthcare System and Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Vivian
authors: V
authors: Cristofaro
authors: Division of Medicine, VA Boston Healthcare System and Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Josephine A
authors: JA
authors: Carew
authors: Division of Medicine, VA Boston Healthcare System and Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Raj K
authors: RK
authors: Goyal
authors: Division of Urology, VA Boston Healthcare System and Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Maryrose P
authors: MP
authors: Sullivan
mesh_terms: D000818:Animals; D005748:Gastric Fundus / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000172:deficiency / Q000378:metabolism*; D024701:Myosin Type V / Q000172:deficiency / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010413:Penis / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
chemical_list: C513082:Myo5a protein, mouse; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D024701:Myosin Type V; D018995:Myosin Heavy Chains; D019331:NG-Nitroarginine Methyl Ester