Role of Rho in rabbit parietal cell.
Rho is known as an important regulator of actin microfilament formation. We were led to study it because a dynamic rearrangement of actin filaments occurs during activation of gastric acid secretion. In order to use specific probes, the rabbit gastric gland culture system was employed and the various genes were expressed using adenovirus vector. When the constitutive active mutant of Rho (RhoAV14) was expressed, histamine- or carbachol-stimulated acid secretion monitored by (14)C-aminopyrine accumulation was inhibited. Conversely, expression of C3 toxin, the specific inhibitor of Rho, and expression of G(12/13)-specific regulator of G-protein signaling domain, the specific inhibitor of G(12/13) which is considered to be an upstream mediator of Rho, both potentiated acid secretion stimulated by the agonists. F-actin staining of parietal cell expressing RhoAV14 revealed that the microfilament supporting the intracellular canaliculi (not on the basolateral membrane) almost disappeared. No clear changes in the intracellular localization of Rho were observed during stimulation of parietal cell. In resting glands, the endogenous active form of Rho was relatively high, and it decreased during histamine stimulation. The finding that any treatment which inhibit Rho augment acid secretion whereas those that activate Rho inhibit secretion strongly suggests that the Rho-pathway conducts a negatively regulating signal in parietal cell activation, possibly via site-specific regulation of actin microfilaments.
Tashiro
Keiichiro
K
Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo.
Nagao
Taku
T
Kurose
Hitoshi
H
Ichijo
Hidenori
H
Urushidani
Tetsuro
T
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D005822:Genetic Vectors; D006632:Histamine / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D009924:Organ Culture Techniques; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D018679:Cholinergic Agonists; D006632:Histamine; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020741:rho GTP-Binding Proteins