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  • Title: Dual effect of endothelin 1 on angiotensin II-potentiated purinergic neurotransmission in prostatic rat vas deferens.
    Author: Cheng M, Lee SS, Cheung WT.
    Journal: Eur J Pharmacol; 2007 Feb 28; 557(2-3):204-11. PubMed ID: 17196586.
    Abstract:
    Angiotensin and endothelin are vasoactive peptides with neuromodulatory effect, however their interactions in facilitating neurotransmission are largely unknown. In the present study, effort was made to examine how endothelin 1 modulates angiotensin II-potentiated purinergic neurotransmission in prostatic rat vas deferens. Both peptides facilitated field-stimulated muscle contraction in a concentration-dependent manner with Kd values of 16.97+/-6.47 and 2.46+/-0.83 nM for angiotensin II and endothelin 1, respectively. Hill plot analysis gave Hill constants of 0.91+/-0.15 and 0.97+/-0.26 for angiotensin II and endothelin 1, respectively. Correlation analysis indicated that the extent of potentiation by angiotensin II, but not endothelin 1, was proportional to the basal field-stimulated muscle contraction. In the presence of low concentrations of endothelin 1 (< or = 3 nM), angiotensin II-potentiated field-stimulated contraction was further enhanced by endothelin. However, in the presence of high concentrations of endothelin 1 (> or = 10 nM), a much increased basal field-stimulated contraction was observed, and the addition of angiotensin II did not elicit any further enhancement in the contractile response. Intriguingly, after prolonged exposure of prostatic rat vas deferens to a high concentration of endothelin 1, the addition of angiotensin II induced a refractory response to field-stimulation. Taken together, our result indicated that endothelin 1 augmented angiotensin II-facilitated purinergic neurotransmission in prostatic rat vas deferens at low concentrations, but inhibited gradually at high concentrations.
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