Comparative studies on the central effects of the angiotensin II analogue (Sar1 azaVal3 Ile8) AT II.
The effects of the newly-synthesized AT II analogue (Sar1 azaVal3 Ile8) AT II were investigated in comparison with the octapeptide AT II and the analogue saralazin (Sar1 Ala8) AT II, using intracerebroventricular administration, with respect to the following parameters: the level of biogenic monoamines (DA, NA and 5-HT) and the metabolites HVA and 5-HIAA in mouse forebrain; the behaviour of the animals--cataleptogenic actions of mice, PTZ convulsive--seizure threshold in mice, apomorphine stereotypy in rats and behaviour of rats in a conflict situation. The analogue (Sar1 azaVal3 Ile8) AT II, unlike saralazin and AT II, was found to induce a rise in the NA and 5-HT levels, causing also catalepsy that is different from the catalepsy induced by saralazine, AT II and haloperidol, because of its rapid onset and decline; it increases the PTZ convulsive--seizure threshold and reduces the number of punished responses to the conflict drinking test (anxiomimetic effect) in a dose 20 times lower than the dose inducing the remaining effects. This effect was antagonized by saralazine. It is concluded that the newly-synthesized analogue (Sar1 azaVal3 Ile8) AT II induces effects similar to those caused by AT II, being at the same time different to a certain extent from the effects (quantitative and qualitative) of octapeptide AT II.
Georgiev
V P
VP
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
Klusha
V E
VE
Getova
D P
DP
Petkov
V D
VD
Svirskis
S V
SV
Mutsenietse
R K
RK
Kambourova
T S
TS
Oppitz
M Zh
MZh
Ancans
J E
JE
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced; D003220:Conflict, Psychological; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D051381:Rats; D012504:Saralasin / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013239:Stereotyped Behavior / Q000187:drug effects
D001679:Biogenic Amines; D000804:Angiotensin II; C056879:angiotensin II, Sar(1)-aza-Val(3)-Ile(8)-; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D012504:Saralasin; D001058:Apomorphine; D010433:Pentylenetetrazole