Mode of action of ANG II on ion transport in guinea pig distal colon.
The effect of ANG II on mucosal ion transport and localization of ANG type 1 receptor (AT(1)R) in the guinea pig distal colon was investigated. Submucosal/mucosal segments were mounted in Ussing flux chambers, and short-circuit current (I(sc)) was measured as an index of ion transport. Serosal addition of ANG II produced a concentration-dependent (10(-9)-10(-5) M) increase in I(sc). The maximal response was observed at 10(-6) M; the increase in I(sc) was 164.4 +/- 11.8 microA/cm(2). The ANG II (10(-6) M)-evoked response was mainly due to Cl(-) secretion. Tetrodotoxin, atropine, the neurokinin type 1 receptor antagonist FK-888, and piroxicam significantly reduced the ANG II (10(-6) M)-evoked response to 28, 45, 58, and 16% of control, respectively. Pretreatment with prostaglandin E(2) (10(-5) M) resulted in a threefold increase in the ANG II-evoked response. The AT(1)R antagonist FR-130739 completely blocked ANG II (10(-6) M)-evoked responses, whereas the ANG type 2 receptor antagonist PD-123319 had no effect. Localization of AT(1)R was determined by immunohistochemistry. In the immunohistochemical study, AT(1)R-immunopositive cells were distributed clearly in enteric nerves and moderately in surface epithelial cells. These results suggest that ANG II-evoked electrogenic Cl(-) secretion may involve submucosal cholinergic and tachykinergic neurons and prostanoid synthesis pathways through AT(1)R on the submucosal plexus and surface epithelial cells in guinea pig distal colon.
Hosoda
Y
Y
Laboratory of Environmental Physiology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Winarto
A
A
Iwanaga
T
T
Kuwahara
A
A
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006834:Hydrazines / Q000494:pharmacology; D007150:Immunohistochemistry; D007477:Ions; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010077:Oxazepines / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D002712:Chlorides; D006834:Hydrazines; D007477:Ions; D064729:Neurokinin-1 Receptor Antagonists; D010077:Oxazepines; D011448:Prostaglandin Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D002034:Bumetanide; D000804:Angiotensin II; C086836:SC 51089; D013779:Tetrodotoxin; D001285:Atropine; D015232:Dinoprostone