title: Dual effect of endothelin 1 on angiotensin II-potentiated purinergic neurotransmission in prostatic rat vas deferens.
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.
authors.affiliation: Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Man
authors.initials: M
authors.lastname: Cheng
authors.forename: Susanna S T
authors.initials: SS
authors.lastname: Lee
authors.forename: Wing-Tai
authors.initials: WT
authors.lastname: Cheung
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011467:Prostate / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology
chemical_list: D019332:Endothelin-1; D018048:Receptors, Purinergic P2; D000804:Angiotensin II