Journal of Smooth Muscle Research最新文献

Aim: Some amino acids been known to influence gastric emptying. Thus we have evaluated the effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying.

Materials and methods: Gastric emptying was evaluated in rats after feeding with Racol (nutrient formulae) containing [1-(13)C] acetic acid. Using a breath test, the content of (13)CO2 in their expired air was measured by infrared analyzers. Rats were orally administered with test amino acids, while control rats were administered orally with distilled water.

Results: The expired (13)CO2 content in the expired air increased with time, peaked after about 30 min and decreased thereafter. Among the amino acids having an alkyl chain, L-serine, L-alanine and L-glycine, significantly decreased the (13)CO2 content and Cmax, and delayed Tmax, suggesting inhibition and delay of gastric emptying. AUC(120min) values of L-alanine and L-glycine also decreased significantly. L-Threonine significantly decreased (13)CO2 content and delayed Tmax, but had no influence on Cmax and AUC(120min) values, suggesting a delay of gastric emptying. L-Isoleucine and L-leucine and L-valine significantly decreased (13)CO2 content, suggesting inhibition of the gastric emptying, but Cmax, Tmax and AUC(120min) values were not significantly affected.

Conclusion: The results show that the amino acids used in the present study had different effects on gastric emptying. Moreover, it was found that inhibition and delay of gastric emptying were clearly classifiable by analyzing the change in (13)CO2 content of the expired air and the Cmax, Tmax and AUC(120min) values.

The regulation of smooth muscle contraction and relaxation involves phosphorylation and dephosphorylation of regulatory proteins, particularly myosin. To elucidate the regulatory mechanisms, analyzing the phosphorylation signal transduction is crucial. Although a pharmacological approach with selective inhibitors is sensitive and a useful technique, it leads to speculation regarding a signaling pathway but does not provide direct evidence of changes at a molecular level. We developed a highly sensitive biochemical technique to analyze phosphorylation by adapting Phos-tag SDS-PAGE. With this technique, we successfully analyzed myosin light chain (LC20) phosphorylation in tiny renal afferent arterioles. In the rat afferent arterioles, endothelin-1 (ET-1) induced diphosphorylation of LC20 at Ser19 and Thr18 as well as monophosphorylation at Ser19 via ET B receptor activation. Considering that LC20 diphosphorylation can decrease the rate of dephosphorylation and thus relaxation, we concluded that LC20 diphosphorylation contributes, at least in part, to the prolonged contraction induced by ET-1 in the renal afferent arteriole.

Aim: The present study aimed to evaluate the effects of selected straight alkyl chain, hydroxylated chain and branched chain amino acids on gastric adaptive relaxation, as these have previously been shown to have differing effects on gastric emptying.

Materials and methods: Gastric adaptive relaxation was evaluated using a barostat in rats under urethane anesthesia. The pressure within the balloon, introduced from the mouth to the stomach, was changed stepwise from 1 to 8 mmHg. The increased volume just after the increase of balloon pressure was defined as distension-induced gastric adaptive relaxation (accommodation). Amino acids were administered orally or intravenously.

Results: As compared with control rats administered with distilled water, those rats that were orally administered amino acids having straight alkyl chain and extra hydroxylated alkyl chain, such as glycine and l-serine, had significantly enhanced gastric adaptive relaxation, but administration of l-alanine and l-threonine did not. Branched chain amino acids, such as l-isoleucine, l-leucine and l-valine, also did not significantly influence gastric adaptive relaxation. Glycine and l-serine showed the same efficacy when administered intravenously.

Conclusion: Among the amino acids evaluated in the present study, glycine and l-serine significantly enhanced gastric adaptive relaxation, suggesting that short alkyl chain amino acids may enhance gastric adaptive relaxation as compared with the other amino acids. These findings may suggest that glycine and l-serine would be useful in the therapy of functional dyspepsia, especially for early satiety, because the dysfunction of adaptive relaxation is one of the causes of early satiety.

Uridine triphosphate (UTP) can be released from damaged cells to cause vasoconstriction. Although UTP is known to act through P2Y receptors and PLC activation in vascular smooth muscle, the role of PKC in generating the response is somewhat unclear. Here we have used Tat-linked membrane permeable peptide inhibitors of PKC to assess the general role of PKC and also of specific isoforms of PKC in the UTP induced contraction of rat mesenteric artery. We examined the effect of PKC inhibition on UTP induced contraction, increased cytoplasmic Ca(2+) and reduction of K(+) currents and found that PKC inhibition caused a relatively small attenuation of contraction but had little effect on changes in cytoplasmic Ca(2+). UTP attenuation of both voltage-gated (Kv) and ATP-dependent (KATP) K(+) currents was abolished when intracellular Ca(2+) was decreased from 100 to 20 nM. PKC inhibition reduced slightly the ability of UTP to attenuate Kv currents but had no effect on KATP current inhibition. In conclusion, both UTP induced contraction of mesenteric artery and the inhibition of Kv and KATP currents of mesenteric artery smooth muscle cells by UTP are relatively independent of PKC activation; furthermore, the inhibition of both Kv and KATP currents requires intracellular Ca(2+).