α1L-adrenoceptors mediate contraction of human erectile tissue
α1-adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly α1A-adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the α1L-adrenoce...
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Elsevier,
2018-08-01T00:00:00Z.
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|---|---|---|---|
| 001 | doaj_a2e5779efeef4de4baf1c91db8a1661d | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Beverley J. Davis |e author |
| 700 | 1 | 0 | |a Christopher R. Chapple |e author |
| 700 | 1 | 0 | |a Donna J. Sellers |e author |
| 700 | 1 | 0 | |a Alisdair L. Naylor |e author |
| 700 | 1 | 0 | |a David Sillar |e author |
| 700 | 1 | 0 | |a Alistair Campbell |e author |
| 700 | 1 | 0 | |a Russ Chess-Williams |e author |
| 245 | 0 | 0 | |a α1L-adrenoceptors mediate contraction of human erectile tissue |
| 260 | |b Elsevier, |c 2018-08-01T00:00:00Z. | ||
| 500 | |a 1347-8613 | ||
| 500 | |a 10.1016/j.jphs.2018.08.003 | ||
| 520 | |a α1-adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly α1A-adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the α1L-adrenoceptor. Functional experiments using subtype selective agonists and antagonists, along with radioligand ([3H]tamsulosin) binding assays, were used to determine the α1-adrenoceptor population. A61603, a α1A-adrenoceptor agonist, was a full agonist with a potency 21-fold greater than that of noradrenaline. The α1A- and α1D-adrenoceptor antagonist tamsulosin antagonized noradrenaline responses with high affinity (pKD = 9.7 ± 0.3), whilst BMY7378 (100 nM) (α1D-adrenoceptor antagonist) failed to antagonize responses. In contrast, relatively low affinity estimates were obtained for both prazosin (pKD = 8.2 ± 0.1) and RS17053 (pKD = 6.9 ± 0.2), antagonists which discriminate between the α1A- and α1L-adrenoceptors. [3H]Tamsulosin bound with high affinity to the receptors of human erectile tissue (pKD = 10.3 ± 0.1) with a receptor density of 28.1 ± 1.4 fmol mg−1 protein. Prazosin displacement of [3H]tamsulosin binding revealed a single homogenous population of binding sites with a relatively low affinity for prazosin (pKi = 8.9). Taken together these data confirm that the receptor mediating contraction in human erectile tissue has the pharmacological properties of the α1L-adrenoceptor. Keywords: Erectile tissue, α1-adrenoceptor subtypes, α1L-adrenoceptor, Tamsulosin, Prazosin | ||
| 546 | |a EN | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Journal of Pharmacological Sciences, Vol 137, Iss 4, Pp 366-371 (2018) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S1347861318301348 | |
| 787 | 0 | |n https://doaj.org/toc/1347-8613 | |
| 856 | 4 | 1 | |u https://doaj.org/article/a2e5779efeef4de4baf1c91db8a1661d |z Connect to this object online. |