Angiotensin II inhibits cortical cholinergic function: implications for cognition.
In the present studies we have shown that angiotensin II (AT II), in a concentration-dependent manner in rat tissue (10(-9)-10(-5) M) or at a single concentration in human tissue (10(-6) M), can inhibit potassium-stimulated release of [3H]acetylcholine ( [3H]Ach) from slices of rat entorhinal cortex and human temporal cortex preloaded with [3H]choline for the biochemical analyses. The inhibitory effects of AT II (10(-6) M) were antagonised by the specific AT II receptor antagonist [1-sarcosine, 8-threonine]AT II in a concentration-dependent manner in rat tissue (10(-11)-10(-8) M) and at the single concentration employed in the human studies (10(-7) M). Also demonstrated were other components of the angiotensin system in the human temporal cortex; ACE activity was present (1.03 nmol min-1 mg-1 protein), as were AT II recognition sites (Bmax = 8.6 fmol mg-1 protein). It is hypothesised that the potential cognitive enhancing properties of ACE inhibitors may reflect their action to prevent the formation of AT II and so remove an inhibitory modulator of cholinergic function.
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, England.
J M
JM
Barnes
N M
NM
Barnes
B
B
Costall
Z P
ZP
Horovitz
J W
JW
Ironside
R J
RJ
Naylor
T J
TJ
Williams
D000109:Acetylcholine / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D005260:Female; D007457:Iodine Radioisotopes; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D007457:Iodine Radioisotopes; D000804:Angiotensin II; D000109:Acetylcholine; D011188:Potassium