α1A-Adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries

Morton, J.S., Daly, C.J. , Jackson, V.M. and McGrath, J.C. (2007) α1A-Adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries. British Journal of Pharmacology, 150(1), pp. 112-120.

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Abstract

<i>Background</i> <i>and</i> <i>purpose</i>: Maintained penile erection depends on the absence of α-adrenoceptor (α-AR) activation and so can be facilitated by α-blockers. This study seeks the α<sub>1</sub>-AR subtypes involved in order to inform the pro-erectile consequences of subtype selective blockade. <i>Experimental</i> <i>approach</i>: Wire myography was used with dorsal (nutritional supply) and cavernous (erectile inflow) penile arteries; standard α-AR-selective agonists and antagonists were employed to classify responses. <i>Key results</i>: In both penile arteries noradrenaline (NA) and phenylephrine (PE, α<sub>1</sub>-AR agonist) caused concentration-dependent contractions. Sensitivity to NA was increased by NA uptake blockers, cocaine (3 μM) and corticosterone (30 μM). PE responses were antagonised by phentolamine (non-selective α-AR: dorsal pK<sub>B</sub> 8.00, cavernous 8.33), prazosin (non-subtype-selective α<sub>1</sub>-AR: dorsal 8.60, cavernous 8.41) and RS100329 (α<sub>1A</sub>-AR selective: dorsal 9.03, cavernous 8.80) but not by BMY7378 (α<sub>1D</sub>-AR selective: no effect at 1-100 nM) or Rec15/2615 (α<sub>1B</sub>-AR selective: no effect at 1-100 nM). Schild analysis was straightforward in cavernous artery, indicating that PE activates only α<sub>1A</sub>-AR. In dorsal artery Schild slopes were low, though α<sub>1A</sub>-AR was still indicated. Analysis using UK 14,304 and rauwolscine indicated an α<sub>2</sub>-AR component in dorsal artery that may account for low slopes to α<sub>1</sub>-AR antagonists. <i>Conclusions</i> <i>and</i> <i>implications</i>: Penile arteries have a predominant, functional α<sub>1A</sub>-AR population with little evidence of other α<sub>1</sub>-AR subtypes. Dorsal arteries (nutritional supply) also have α<sub>2</sub>-ARs. Thus, α-AR blockers with affinity for α<sub>1A</sub>-AR or α<sub>2</sub>-AR would potentially have pro-erectile properties; the combination of these perhaps being most effective. This should inform the design of drugs to assist/avoid penile erection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Daly, Professor Craig and McGrath, Professor John
Authors: Morton, J.S., Daly, C.J., Jackson, V.M., and McGrath, J.C.
Subjects:R Medicine > RM Therapeutics. Pharmacology
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:British Journal of Pharmacology
ISSN:1476-5381

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