The amino acid composition of angiotensin alters its ability to reduce alcohol consumption in rats.
The voluntary consumption of alcohol has been shown to be reduced by a variety of manipulations which enhance activity in the renin-angiotensin system, including the administration of the bovine form of angiotensin II-[Val5]-ANG II. The present study investigated the relationship between the amino acid composition of angiotensin II and its ability to reduce alcohol intake by administering a number of different forms or fragments of the parent peptide. [Ile5]-Angiotensin II ([Ile5]-ANG II), two endogenous fragments of angiotensin II [( Des-Asp1]-ANG II and [Des-Phe8]-ANG II) were administered subcutaneously in rats across a range of doses. [Ile5]-ANG II reduced alcohol intake at all doses tested between 20 and 400 micrograms/kg while [Des-Asp1]-ANG II reduced alcohol intake only at the 400 micrograms/kg dose. [Des-Phe8]-ANG II had no effect on alcohol intake at any dose tested. Administration of the antagonist [Sar1-Thr8]-ANG II by itself did not enhance alcohol intake. While the pressor and dipsogenic properties of these fragments sometimes correlated with the reduction in alcohol intake they were not a causal factor in decreasing the intake. These results indicate that variations in the peptide composition of angiotensin can significantly alter its ability to reduce the consumption of alcohol.
Ross
A D
AD
Department of Pharmacology, University of Toronto, Ontario, Canada.
Perlanski
E
E
Grupp
L A
LA
D000428:Alcohol Drinking; D000596:Amino Acids / Q000032:analysis*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000596:Amino Acids; D010446:Peptide Fragments; D000804:Angiotensin II; D000805:Angiotensin III; C073465:angiotensin II, des-Phe(8)-; C014805:angiotensin II, Sar(1)-Thr(8)-