Ito cell contraction in response to endothelin-1 and substance P

Abstract

The contractile response of cultured Ito cells to endothelin-1 and substance P was examined. Ito cells were obtained from rat liver by perfusion with collagenase, followed by separation through centrifugal elutriation, and were cultured for 24 hr. The area of the Ito cells was measured after treatment with endothelin-1 or substance P at various concentrations in the culture medium. The area of the cells decreased dose dependently after treatment with endothelin-1 or substance P. The area of Ito cells before addition of interleukin-1 or substance P was defined as 100%. The area of the cells after treatment with endothelin-1 or substance P medium was expressed as the percentage against the area before treatment with endothelin-1 or substance P. The percentage in area after treatment with 200 nmol/L endothelin-1 was as follows: 81% +/- 13% at 30 min, 77% +/- 15% at 60 min, 87% +/- 15% at 120 min and 99% +/- 18% at 180 min. The maximal decrease in area occurred at 60 min after treatment. The percentage values for 200 nmol/L substance P were as follows: 88% +/- 15% at 10 min, 95% +/- 17% at 30 min and 101% +/- 17% at 60 min. The maximal decrease in area was noted at 10 min. Thus Ito cells contracted in response to treatment with endothelin-1 or substance P. The mode of the extent and onset of the contraction was different for the two peptides. These findings suggest that Ito cells are involved in the regulation of the hepatic sinusoidal microcirculation.

Effect of Tetrandrine on Experimental Hepatic Fibrosis Induced by Bile Duct Ligation and Scission in Rats

“…Recent investigation found that voltage-operated calcium channel (VOCC) plays an important role in the regulation of hepatic stellate cells contractility which is the marked phenotype of activated hepatic stellate cells (Berlin 1995;Bataller et al 1998). Moreover, activated hepatic stellate cells have receptors for a number of vasoconstrictor substances such as endotheline, angiotensin II, vasopressin, thrombin and thromboxan A2 (Pinzani et al 1992;Sakamoto et al 1993;Kawada et al 1993;Bataller et al 1997;Rockey 1997). Therefore, it is likely that the inhibitory effect of tetrandrine on hepatic stellate cells activation, at least in part, through the blocking of calcium channels.…”

Atrial natriuretic peptide antagonizes endothelin-induced calcium increase and cell contraction in cultured human hepatic stellate cells

“…Endothelin-1 was selected because of its marked contractile effect for HSCs and its potential pathogenic role in the increased intrahepatic resistance to portal blood flow observed in chronic liver diseases. 6,[9][10][11][12][13][14]39 In the current study, cell contraction was assessed by measuring changes in cell area with a morphometric method. This method was chosen because a large number of studies in different contractile cell types, 40,41 including previous studies from our laboratory in HSCs, 15,26 have used changes in cell area as a reliable tool to evaluate contraction in cultured cells.…”

“…[4][5][6][7][8][9][10] Moreover, HSCs have receptors for a large number of vasoconstrictor substances, including endothelin-1, arginine vasopressin, thrombin, thromboxanes, and angiotensin II. 6,8,[11][12][13][14][15] Finally, the stimulation of HSCs in culture with these vasoconstrictor substances is associated with a marked increase in intracellular calcium concentration ([Ca 2ϩ ] i ) and cell contraction, 6,[8][9][10][11][12][13][14][15] suggesting that the contractile function of HSCs may be regulated by the action of vasoconstrictors.In contractile cells, the effects of vasoconstrictor agonists may be attenuated by the action of vasodilators. In fact, the state of contraction/relaxation of contractile cells is dependent on the interaction between vasoconstrictor and vasodilator factors.…”

The hepatic circulation in health and disease: Report of a single-topic symposium

“…61 Cultured HSC also contract in response to several vasopressive stimuli including thrombin, angiotensin II, ET, substance P, and eicosanoids. [61][62][63] Additionally, the anatomic location of HSC along the hepatic sinusoids is theoretically ideal to regulate blood flow through contraction and relaxation. 59 HSC in vivo exhibit a quiescent phenotype, but can be activated by stimuli such as inflammatory cytokines, growth factors, and changes in extracellular matrix composition.…”