title: Targeted disruption of the A2A adenosine receptor reduces in-vitro prostate contractility in mature mice.
abstract: Prostatic A2A adenosine receptors mediate varied effects. This study aimed to test whether genetic disruption of this receptor affects prostate contractility. Prostates taken from mice which were homozygous (A2AR-/-) and heterozygous (A2AR+/-) for the disrupted A2A adenosine receptor gene and wild-type littermates (A2AR +/+) were mounted in organ baths. Contractile responses to nerve stimulation and noradrenaline were measured in the presence of various pharmacological tools. Electrical field stimulation (0.5 ms pulse duration, 60 V, 0.1-20 Hz) yielded frequency-dependent contractions while exogenous administration of noradrenaline (10 nM-1 mM) or tyramine (1 microM-1 mM) produced concentration-dependent responses. Contractile responses to electrical field stimulation from A2AR-/- and A2AR+/- prostates were reduced when compared to A2A+/+ prostates (P=0.013, n=33-36). Prazosin (0.3 microM) inhibited electrical field stimulation-induced responses in prostates from A2AR+/+ and A2AR+/- mice (P< or =0.016, n=5-7) but not A2AR-/- mice (P=0.400, n=6). Tetrodotoxin abolished electrical field stimulation-induced responses in all prostates (P<0.001, n=5-7). NF 449 and ZM 241385 were without effect (P< or =0.421, n=4-6). There were no genotype differences in noradrenaline or tyramine concentration-response curves (P> or =0.180, n=10-13). Prazosin (0.3 microM) and cocaine (10 microM) attenuated the responses induced by noradrenaline (P<0.001, n=6-7) and tyramine (P<0.001, n=5-6), respectively, in all genotypes. Disruption of the A2A adenosine receptor leads to reduced nerve mediated contractile responses of the prostate in mature mice.
authors.affiliation: Prostate Research Co-operative, Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Gray
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Short
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Sab
authors.initials: S
authors.lastname: Ventura
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005838:Genotype; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects*; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014439:Tyramine / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D043705:Receptor, Adenosine A2A; D013779:Tetrodotoxin; D009638:Norepinephrine; D014439:Tyramine