Prejunctional angiotensin receptors involved in the facilitation of noradrenaline release in mouse tissues.
The effect 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 [3H]-noradrenaline. The prejunctional angiotensin receptor type was investigated using the non-selective receptor antagonist saralasin (AT1/AT2) and the AT1 and AT2 selective receptor antagonists losartan and PD 123319, respectively. In atrial and splenic preparations, angiotensin II (0.01 nM-0.1 microM) and angiotensin III (0.01 and 0.1 nM-1 microM) increased the stimulation-induced overflow of tritium in a concentration-dependent manner. Angiotensin IV, only at high concentrations (1 and 10 pM), enhanced tritium overflow in the atria, while angiotensin-(1-7) (0.1 nM-10 microM) was without effect in both preparations. In preparations of hippocampus, occipito-parietal cortex and hypothalamus, none of the angiotensin peptides altered the evoked overflow of tritium. In atrial and splenic preparations, saralasin (0.1 microM) and losartan (0.1 and 1 microM), but not PD 123319 (0.1 microM), shifted the concentration-response curves of angiotensin II and angiotensin III to the right. In conclusion, in mouse atria and spleen, angiotensin II and angiotensin III facilitate the action potential induced release of noradrenaline via a prejunctional AT1 receptor. Only high concentrations of angiotensin IV are effective in the atria and angiotensin-(1-7) is without effect in both preparations. In mouse brain areas, angiotensin II, angiotensin III, angiotensin IV and angiotensin-(1-7) do not modulate the release of noradrenaline.
Cox
S L
SL
Pharmakologisches Institut, Freiburg University, Germany. coxsandr@sun2.ruf.uni-frieburg.de
Trendelenburg
A U
AU
Starke
K
K
D000804:Angiotensin II / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000502:physiology; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000502:physiology*; D013154:Spleen / Q000378:metabolism
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III; D009638:Norepinephrine