Alpha(1A)-adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries.
OBJECTIVE
Maintained penile erection depends on the absence of alpha-adrenoceptor (alpha-AR) activation and so can be facilitated by alpha-blockers. This study seeks the alpha(1)-AR subtypes involved in order to inform the pro-erectile consequences of subtype selective blockade.


METHODS
Wire myography was used with dorsal (nutritional supply) and cavernous (erectile inflow) penile arteries; standard alpha-AR-selective agonists and antagonists were employed to classify responses.


RESULTS
In both penile arteries noradrenaline (NA) and phenylephrine (PE, alpha(1)-AR agonist) caused concentration-dependent contractions. Sensitivity to NA was increased by NA uptake blockers, cocaine (3 microM) and corticosterone (30 microM). PE responses were antagonised by phentolamine (non-selective alpha-AR: dorsal pK(B) 8.00, cavernous 8.33), prazosin (non-subtype-selective alpha(1)-AR: dorsal 8.60, cavernous 8.41) and RS100329 (alpha(1A)-AR selective: dorsal 9.03, cavernous 8.80) but not by BMY7378 (alpha(1D)-AR selective: no effect at 1-100 nM) or Rec15/2615 (alpha(1B)-AR selective: no effect at 1-100 nM). Schild analysis was straightforward in cavernous artery, indicating that PE activates only alpha(1A)-AR. In dorsal artery Schild slopes were low, though alpha(1A)-AR was still indicated. Analysis using UK 14,304 and rauwolscine indicated an alpha(2)-AR component in dorsal artery that may account for low slopes to alpha(1)-AR antagonists.


CONCLUSIONS
Penile arteries have a predominant, functional alpha(1A)-AR population with little evidence of other alpha(1)-AR subtypes. Dorsal arteries (nutritional supply) also have alpha(2)-ARs. Thus, alpha-AR blockers with affinity for alpha(1A)-AR or alpha(2)-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.
Morton
J S
JS
Autonomic Physiology Unit, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow, UK.
Daly
C J
CJ
Jackson
V M
VM
McGrath
J C
JC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D010413:Penis / Q000098:blood supply*; D010656:Phenylephrine; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine