Adenosine A(3) receptor mediated coronary vasodilation in the rat heart: changes that occur with maturation.
Adenosine A(2B) and A(3) receptors (ADOR) have been reported to induce coronary vasodilation in the rat. This study investigated the effect of age on ADORA(3) mediated coronary responses using hearts from rats aged 6-8 weeks (immature), 16-18 weeks (young) and 52-54 weeks (mature) perfused in Langendorff mode. APNEA (ADORA(3)>ADORA(1) agonist) was observed to activate at least two receptor subtypes to mediate a biphasic vasodilator response in hearts from immature rats. The potency of APNEA at the high affinity site was enhanced by alloxazine (ADORA(2B) antagonist) and reduced when combined with MRS1191 (ADORA(3) antagonist). This indicates that the high affinity phase is the ADORA(3), and ADORA(2B) signalling is likely to play a negative regulatory role towards the ADORA(3) mediated response. The activity at this site was also reduced with maturation. The low affinity site was inhibited by alloxazine but not MRS1191, indicating that this response is mediated by the ADORA(2B) or another receptor subtype. The response at this site did not alter with age. Cl-IB-MECA (ADORA(3) agonist) produced monophasic responses that were inhibited by alloxazine but remained unaffected by MRS1191 in all age groups. In addition the potency of Cl-IB-MECA does not change in hearts from PTX-treated rats. However, the maximal responses increased, indicating G(i) protein independent and dependent signalling. Q-PCR analysis of rat hearts indicated the presence of an ADORA(3) splice variant (ADORA(3i)), which increased in mRNA expression with age. Cl-IB-MECA responses may be mediated by this ADORA(3i). In conclusion, APNEA mediates coronary vasodilation in the rat heart via at least two receptor sites, the ADORA(3) and ADORA(2B). ADORA(3) responses are reduced while ADORA(2B) remain unchanged with maturation. In addition, the splice variant ADORA(3i) may contribute to coronary responses in the rat heart.
Jenner
Tamsin L
TL
School of Medical Science, Griffith University Gold Coast Campus, Southport, Qld 9726, Australia. t.jenner@griffith.edu.au
Rose'meyer
Roselyn B
RB
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists; D000375:Aging / Q000502:physiology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D008297:Male; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D058909:Adenosine A3 Receptor Agonists; D004095:Dihydropyridines; C107728:MRS 1191; C086112:N(6)-2-(4-aminophenyl)ethyladenosine; D043684:Receptor, Adenosine A3; D000241:Adenosine