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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cox, S. L. Lau, W. A. Pennefather, J. N. Mitchelson, F. J. |
| Description | Author Affiliation: Lau WA ( Department of Pharmacology, Monash University, Clayton, Victoria, Australia.) |
| Abstract | Experiments have been conducted to investigate the actions of endothelins on the guinea-pig prostate gland. Saturation experiments with [125I]-endothelin-1 (2-800 pM) in guinea-pig prostatic homogenates indicated the presence of high affinity binding sites with an equilibrium dissociation constant (KD) of 230+/-50 pM, a maximum number of binding sites (Bmax) of 52+/-16 fmol mg(-1) protein or 269+/-61 fmol g(-1) tissue and a Hill coefficient (nH) of 1.01+/-0.03 (n = 3). Competition experiments revealed that binding of [125I]-endothelin-1 (20 pM) was inhibited with the following order of potency: endothelin-1 >>BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl-Leu-D-Trp[1-+ ++CO2CH3-D-Nle-ONa])> BQ-123 (cyclo-D-Asp-L-Pro-D-Val-Leu-D-Trp) > or = sarafotoxin S6c. At concentrations with negligible influence on smooth muscle tone, endothelin-1, endothelin-2 and sarafotoxin S6b (1 nM-0.1 microM) produced concentration-dependent potentiation of the contractions evoked by electrical field stimulation with trains of 20 pulses at 10 Hz every 50 s, 0.5 ms pulse width and a dial setting of 60 V. In contrast, the endothelin ET(B) receptor-preferring agonist endothelin-3 (1 nM- 1 microM) was much less potent, and the endothelin ET(B) receptor-selective agonists sarafotoxin S6c and BQ-3020 (Ac-[Ala11,15]-endothelin-1 (6-21)), up to 1 microM, were without effect. The endothelin ET(A) receptor antagonist BQ-123 (1 microM) markedly inhibited the potentiation induced by endothelin-1, endothelin-2 and sarafotoxin S6b while the endothelin ET(B) receptor antagonist BQ-788 (1 microM) was less effective. While our binding data indicates the presence of ET(A) and ET(B) binding sites in the guinea-pig prostate, the endothelin-induced facilitation of neurotransmission to the prostatic smooth muscle is mediated largely via activation of endothelin receptors of the ET(A) subtype. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 127 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Prostate Drug Effects Receptors, Endothelin Animals Binding, Competitive Dose-Response Relationship, Drug Endothelin-1 Metabolism Guinea Pigs Muscle Contraction Oligopeptides Pharmacology Peptides, Cyclic Piperidines Physiology Radioligand Assay Receptor, Endothelin A Receptor, Endothelin B Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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