Prejunctional angiotensin receptors involved in the facilitation of noradrenaline release in mouse tissues

Abstract

1 The e ect of angiotensin II, angiotensin III, angiotensin IV and angiotensin-(1 ± 7) on the electrically induced release of noradrenaline was studied in preparations of mouse atria, spleen, hippocampus, occipito-parietal cortex and hypothalamus preincubated with [ 3 H]-noradrenaline. The prejunctional angiotensin receptor type was investigated using the non-selective receptor antagonist saralasin (AT 1 /AT 2 ) and the AT 1 and AT 2 selective receptor antagonists losartan and PD 123319, respectively. 2 In atrial and splenic preparations, angiotensin II (0.01 nM ± 0.1 mM) and angiotensin III (0.01 and 0.1 nM ± 1 mM) increased the stimulation-induced over¯ow of tritium in a concentration-dependent manner. Angiotensin IV, only at high concentrations (1 and 10 mM), enhanced tritium over¯ow in the atria, while angiotensin-(1 ± 7) (0.1 nM ± 10 mM) was without e ect in both preparations. 3 In preparations of hippocampus, occipito-parietal cortex and hypothalamus, none of the angiotensin peptides altered the evoked over¯ow of tritium. 4 In atrial and splenic preparations, saralasin (0.1 mM) and losartan (0.1 and 1 mM), but not PD 123319 (0.1 mM), shifted the concentration-response 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 AT 1 receptor. Only high concentrations of angiotensin IV are e ective in the atria and angiotensin-(1 ± 7) is without e ect in both preparations. In mouse brain areas, angiotensin II, angiotensin III, angiotensin IV and angiotensin-(1 ± 7) do not modulate the release of noradrenaline.

Postnatal development of presynaptic receptors that modulate noradrenaline release in mice

“…Facilitatory angiotensin AT 1 receptors occur in atria and the vas deferens (but not the hippocampus and the occipito-parietal cortex) of adult mice (Cox et al 1999;S.L. Cox, unpublished observations).…”

“…Values are means± SEM from 7-22 superfusion chambers. Experiments on adults (A) are from Cox et al (1999) …”

“…Presynaptic heteroreceptors have recently been studied systematically in mice (Cox et al 1999;Trendelenburg et al 2000). The present work shows that most of the receptors undergo a change of function with age.…”

“…The brain, heart or vasa deferentia were removed and placed in ice-cold physiological salt solution (PSS) saturated with 5% CO 2 in O 2 . Preparation of adult mouse tissues has been described previously: from one adult mouse 15-30 slices of the hippocampus, 6-7 slices of the occipitoparietal cortex, 6-8 pieces of the atria and 12-14 pieces of the vasa deferentia were obtained (Cox et al 1999;Trendelenburg et al 2000). From each P1 mouse, 2 round slices, 0.3 mm thick, of the occipito-parietal cortex, the two hippocampi, the right and left atria, and the two vasa deferentia (males) were used.…”

“…All occur in at least some tissues of adult mice (Cox et al 1999;Trendelenburg et al 2000;Zhou et al 2001). Presynaptic β 2 -adrenoceptors are reckoned among the heteroreceptors here because they do not fully satisfy the autoreceptor definition (p. 872 of Starke et al 1989).…”