Endothelin receptors and their cellular signal transduction mechanism in human cultured prostatic smooth muscle cells

Abstract

1. Endothelin (ET) receptors, and their cellular signal transduction mechanism, were characterized in a primary culture of human prostatic smooth muscle cells (HP cell).

2. [¹²⁵I]-ET-1 and [¹²⁵I]-ET-3 binding studies revealed that both ET_A and ET_B receptors were present in the HP cells, and the ratio of ET_A to ET_B receptors was 1.4:1.

3. Analysis of ET receptor mRNA by reverse transcription-polymerase chain reaction also demonstrated that HP cells express both ET_A and ET_B receptors.

4. ET-1 and ET-3 increased intracellular free Ca²⁺ concentration ([Ca²⁺]_i) in the HP cells in a concentration-dependent manner. Use of subtype selective antagonists BQ-123 and BQ-788, indicated that both ET_A and ET_B receptors were coupled to an increase in [Ca²⁺]_i.

5. Pretreatment of the cells with pertussis toxin resulted in a significant but partial attenuation of the [Ca²⁺]_i increase mediated through the ET_A and ET_B receptors. However, sensitivity to pertussis toxin (PTX) was significantly different between them.

6. In conclusion, HP cells possess ET_A and ET_B receptors. Further, these two endothelin receptor subtypes evoke an increase in [Ca²⁺]_i possibly via the action of different GTP-binding proteins.

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