Vasopressin stimulates ciliary motility of rabbit tracheal epithelium: role of V1b receptor-mediated Ca2+ mobilization.
Arginine vasopressin (AVP) has recently been shown to exist in and to be released from airway epithelial cells, but the physiologic role of this hormone in airway epithelial function is unknown. To determine whether AVP affects ciliary motility, and if so, to elucidate the mechanism of action and the subtype of AVP receptors involved, we measured ciliary beat frequency (CBF) and the intracellular Ca2+ concentration ([Ca2+]i) of cultured rabbit tracheal epithelium with a photoelectric method and the fura-2 fluorescence method, respectively. Addition of AVP caused a rapid increase in CBF, followed by a decline and a subsequent sustained response. The ciliary stimulatory action was dose dependent, the maximal peak increase from the baseline CBF being 20.6 +/- 4.7% (mean +/- SE, P < 0.001), and this effect was reduced to 5.9 +/- 2. 0% by the V1 receptor antagonist OPC-21268 (P < 0.01), but not by the V2 receptor antagonist OPC-31260. The AVP-induced increase in CBF was not altered by the protein kinase A (PKA) inhibitor Rp-adenosine-3',5'-cyclic monophosphorothioate triethylamine (Rp-cAMPS) or by Ca2+-free solution containing ethylene glycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), but was abolished by pretreatment with thapsigargin. Exposure of cells to AVP elicited a transient increase in [Ca2+]i, an effect that was likewise abolished by thapsigargin. The rank-order potency of AVP analogues to increase [Ca2+]i was AVP = [deamino1, D-3-(pyridyl) Ala2-Arg8] vasopressin (DP-VP), a specific V1b receptor agonist > [Phe2, Ile3, Orn8] vasopressin (PO-VT), a V1a agonist > 1-desamino-8-D-arginine vasopressin (dDAVP), a V2 agonist. Moreover, OPC-21268 greatly attenuated the action of AVP, whereas OPC-31260 was without effect. These results suggest that AVP stimulates ciliary motility of rabbit tracheal epithelium through mobilization of Ca2+ from thapsigargin-sensitive stores, and that this effect may be mediated by V1b receptors.
First Department of Medicine, Tokyo Women's Medical College, Tokyo, Japan.
J
J
Tamaoki
M
M
Kondo
S
S
Takeuchi
H
H
Takemura
A
A
Nagai
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002923:Cilia / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D011817:Rabbits; D017483:Receptors, Vasopressin / Q000819:agonists / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D002118:Calcium