Sl. Cox et al., Prejunctional angiotensin receptors involved in the facilitation of noradrenaline release in mouse tissues, BR J PHARM, 127(5), 1999, pp. 1256-1262
1 The effect of angiotensin II, angiotensin III, angiotensin IV and angiote
nsin-(1-7) on the electrically induced release of noradrenaline was studied
in preparations of mouse atria, spleen, hippocampus, occipito-parietal cor
tex and hypothalamus preincubated with [H-3]-noradrenaline, The prejunction
al angiotensin receptor type was investigated using the non-selective recep
tor antagonist saralasin (AT(1)/AT(2)) and the AT(1) and AT(2) selective re
ceptor antagonists losartan and PD 123319, respectively.
2 In atrial and splenic preparations, angiotensin II (0.01 nM-0.1 mu M) and
angiotensin III (0.01 and 0.1 nM-1 mu M) increased the stimulation-induced
overflow of tritium in a concentration-dependent manner. Angiotensin IV, o
nly at high concentrations (1 and 10 mu M), enhanced tritium overflow in th
e atria, while angiotensin-(1-7) (0.1 nM-10 mu M) was without effect in bot
h preparations.
3 In preparations of hippocampus, occipito-parietal cortex and hypothalamus
, none of the angiotensin peptides altered the evoked overflow of tritium.
4 In atrial and splenic preparations, saralasin (0.1 mu M) and losartan (0.
1 and 1 mu M), but not PD 123319 (0.1 mu M), shifted the concentration-resp
onse curves of angiotensin II and angiotensin III to the right.
5 In conclusion, in mouse atria and spleen, angiotensin II and angiotensin
III facilitate the action potential induced release of noradrenaline via a
prejunctional ATI receptor. Only high concentrations of angiotensin TV are
effective in the atria and angiotensin-(1-7) is without effect in both prep
arations. In mouse brain areas, angiotensin II, angiotensin III, angiotensi
n IV and angiotensin-(1-7) do not modulate the release of noradrenaline.