Potentiation of cholinergic transmission in the rat hippocampus by angiotensin IV and LVV-hemorphin-7

Recent evidence demonstrates that the fragment of angiotensin II, angiotensin II (3–8) termed angiotensin IV, binds with high affinity to a specific binding site, the AT 4 receptor. Intracerebroventricular injection of AT 4 receptor agonists improves the performance of rats in passive avoidance and spatial learning paradigms. AT 4 receptors and cholinergic neurons are closely associated in regions involved in cognitive processing, such as the hippocampus and neocortex. We therefore postulated that AT 4 receptors affect cognitive processing by modulating cholinergic neurotransmission. To test this, we examined the effect of AT 4 receptor ligands, angiotensin IV and LVV-hemorphin-7, on potassium-evoked [ 3H]acetylcholine ([ 3H]ACh) release from rat hippocampal slices. Hippocampal slices from male Sprague–Dawley rats were incubated with [ 3H]choline chloride, perfused with Krebs–Henseleit solution and [ 3H]ACh release was determined. Angiotensin IV and LVV-hemorphin-7 both potentiated depolarisation-induced [ 3H]ACh release from the rat hippocampus in a concentration-dependent manner with the maximal dose (10 −7M) of each inducing an increase of 45±7.5% ( P