TY  - JOUR
AB  - Reperfusion of ischaemic rat or mouse hearts causes NE [noradrenaline ('norepinephrine')] release, stimulation of ?1-ARs (?1-adrenergic receptors), PLC (phospholipase C) activation, Ins(1,4,5)P3 generation and the development of arrhythmias. In the present study, we examined the effect of increased ?1A-AR drive on these responses. In hearts from non-transgenic mice (?1A- WT), Ins(1,4,5)P3 generation was observed after 2 min of reperfusion following 30 min of zero-flow ischaemia. No Ins(1,4,5)P3 response was observed in hearts from transgenic mice with 66-fold overexpression of ?1A-AR (?1A-TG). This was despite the fact that ?1A-TG hearts had 8-10-fold higher PLC responses to NE than ?1A-WT under normoxic conditions. The immediate phospholipid precursor of Ins(1,4,5)P3, PtdIns(4,5)P2, responded to ischaemia and reperfusion similarly in ?1A-WT and ?1A-TG mice. Thus the lack of Ins(1,4,5)P3 generation in ?1A-TG mice is not caused by limited availability of PtdIns(4,5)P2. Overall, ?1-AR-mediated PLC activity was markedly enhanced in ?1A-WT mice under reperfusion conditions, but responses in ?1A-TG mice were not significantly different in normoxia and post-ischaemic reperfusion. Ischaemic preconditioning prevented Ins(1,4,5)P3 generation after 30 min of ischaemic insult in ?1A-WT mice. However, the precursor lipid PtdIns(4,5)P2 was also reduced by preconditioning, whereas heightened ?1A-AR activity did not influence PtdIns(4,5)P2 responses in reperfusion. Thus preconditioning and ?1A-AR overexpression have different effects on early signalling responses, even though both prevented Ins(1,4,5)P3 generation. These studies demonstrate a selective inhibitory action of heightened ?1A-AR activity on immediate post-receptor signalling responses in early post-ischaemic reperfusion. © The Authors.
AU  - Amirahmadi, F
AU  - Turnbull, L
AU  - Du, XJ
AU  - Graham, RM
AU  - Woodcock, EA
DA  - 2008/01/01
DO  - 10.1042/CS20070110
EP  - 164
JO  - Clinical Science
PY  - 2008/01/01
SP  - 157
TI  - Heightened ?<inf>IA</inf>-adrenergic receptor activity suppresses ischaemia/reperfusion-induced Ins(1,4,5)P<inf>3</inf> generation in the mouse heart: A comparison with ischaemic preconditioning
VL  - 114
Y1  - 2008/01/01
Y2  - 2026/07/11
ER  -