Excitatory regulation of angiotensin II on gastric motility and its mechanism in guinea pig.
In the present study, we investigated the effect of Ang II on gastric smooth muscle motility and its mechanism using intracellular recording and whole-cell patch clamp techniques. Ang II dose-dependently increased the tonic contraction and the frequency of spontaneous contraction in the gastric antral circular smooth muscles of guinea pig. ZD7155, an Ang II type 1 receptor (AT(1)R) blocker, completely blocked the effect of Ang II on the spontaneous contraction of gastric smooth muscle. In contrast, TTX, a sodium channel blocker, failed to block the effect. Furthermore, nicardipine, a voltage-gated Ca(2+)-channel antagonist, did not block the effect of Ang II on the tonic contraction of gastric smooth muscle, but external free-calcium almost completely blocked this effect. Both ryanodine, an inhibitor of calcium-induced Ca(2+) release (CICR) from ryanodine-sensitive calcium stores, and thapsigargin, which depletes calcium in calcium stores, almost completely blocked the effect of Ang II on tonic contraction. However, 2-APB, an inositol trisphosphate (IP(3)) receptor blocker, significantly, but not completely, blocked the Ang II effect on tonic contraction. We also determined that Ang II depolarized membrane potential and increased slow wave frequency in a dose-dependent manner. It also inhibited delayed rectifying potassium currents in a dose-dependent manner, but did not affect L-type calcium currents or calcium-activated potassium currents. These results suggest that Ang II plays an excitatory regulation in gastric motility via AT(1)R-IP(3) and the CICR signaling pathway. The Ang II-induced inhibition of delayed rectifying potassium currents that depolarize membrane potential is also involved in the potentiation of tonic contraction and the frequency of spontaneous contraction in the gastric smooth muscle of guinea pig.
Department of Physiology, Shanghai Jiaotong University School of Medicine, 800 Dongchuan Road, 328# Wenxuan Medical Building, Shanghai, 200240, China.
Hong-Li
HL
Lu
Zuo-Yu
ZY
Wang
Xu
X
Huang
Yan-Fei
YF
Han
Yi-Song
YS
Wu
Xin
X
Guo
Yong-Chul
YC
Kim
Wen-Xie
WX
Xu
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011706:Pyloric Antrum / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D002118:Calcium