α1L-adrenoceptors mediate contraction of human erectile tissue

Beverley J. Davis, Christopher R. Chapple, Donna J. Sellers, Alisdair L. Naylor, David Sillar, Alistair Campbell, Russ Chess-Williams

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Abstract

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.

Original languageEnglish
Pages (from-to)366-371
Number of pages6
JournalJournal of Pharmacological Sciences
Volume137
Issue number4
DOIs
Publication statusPublished - 1 Aug 2018

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tamsulosin
Adrenergic Receptors
Prazosin
A 61603
Norepinephrine
Erectile Dysfunction
Population
Binding Sites
Pharmacology
Phenotype

Cite this

Davis, Beverley J. ; Chapple, Christopher R. ; Sellers, Donna J. ; Naylor, Alisdair L. ; Sillar, David ; Campbell, Alistair ; Chess-Williams, Russ. / α1L-adrenoceptors mediate contraction of human erectile tissue. In: Journal of Pharmacological Sciences. 2018 ; Vol. 137, No. 4. pp. 366-371.
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abstract = "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.",
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α1L-adrenoceptors mediate contraction of human erectile tissue. / Davis, Beverley J.; Chapple, Christopher R.; Sellers, Donna J.; Naylor, Alisdair L.; Sillar, David; Campbell, Alistair; Chess-Williams, Russ.

In: Journal of Pharmacological Sciences, Vol. 137, No. 4, 01.08.2018, p. 366-371.

Research output: Contribution to journalArticleResearchpeer-review

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