title: Role of vasopressin V(₁A) receptor in the urethral closure reflex in rats.
abstract: An enhanced urethral closure reflex via the spinal cord is related to urethral resistance elevation during increased abdominal pressure. However, with the exception of monoamines, neurotransmitters modulating this reflex are not understood. We investigated whether the vasopressin V(₁A) receptor (V(₁A)R) is involved in the urethral closure reflex in urethane-anesthetized female rats. V(₁A)R mRNA was highly expressed among the vasopressin receptor family in the total RNA purified from lamina IX in the spinal cord L6-S1 segment. In situ hybridization analysis of the spinal L6-S1 segment confirmed that these positive signals from the V(₁A)Rs were only detected in lamina IX. Intrathecally injected Arg⁸-vasopressin (AVP), an endogenous ligand, significantly increased urethral resistance during an intravesical pressure rise, and its effect was blocked by the V(₁A)R antagonist. AVP did not increase urethral resistance in rats in which the pelvic nerves were transected bilaterally. Urethral closure reflex responses to the intravesical pressure rise increased by up to threefold compared with the baseline response after AVP administration in contrast to no increase by vehicle. In addition, intravenously and intrathecally injected V(₁A)R antagonists decreased urethral resistance. These results suggest that V(₁A)R stimulation in the spinal cord enhances the urethral closure reflex response, thereby increasing urethral resistance during an abdominal pressure rise and that V(₁A)R plays a physiological role in preventing urine leakage.
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company, Limited, Osaka, Japan. Ueno_Hiroyuki@takeda.co.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ueno
authors.forename: Masako
authors.initials: M
authors.lastname: Kuno
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shintani
authors.forename: Izumi
authors.initials: I
authors.lastname: Kamo
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D017403:In Situ Hybridization; D007211:Indoles / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014521:Urethra / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D007211:Indoles; D011759:Pyrrolidines; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C082134:relcovaptan