The effect of the putative AT2 agonist, p-aminophenylalanine6 angiotensin II, on thirst and sodium appetite in rats.
Intracerebroventricular injection of the putative AT2 agonist, p-aminophenylalanine6 angiotensin II (p-NH2Phe6-Ang II), caused dose-dependent increases in intakes of water and NaCl similar to those produced by angiotensin II but requiring more than one thousand times the dose. Very large doses of another AT2 agonist, angiotensin(1-7) heptapeptide (Ang(1-7)), had no effect on intakes of water and NaCl up to 24 h after injection, nor did Ang(1-7) affect angiotensin II-induced drinking when the two peptides were given together. The AT1 antagonist, losartan, but not the AT2 antagonist, CGP 42112B, inhibited p-NH2Phe6-Ang II- and angiotensin II-induced drinking, suggesting that p-NH2Phe6-Ang II, like angiotensin II, acts on AT1 but not AT2 receptors. However, large doses of the AT2 antagonist, PD 123319, inhibited drinking in response to both dipsogens. Since p-NH2Phe6-Ang II- and angiotensin II-induced drinking were unaffected by CGP 42112B, this could mean that there are different AT2 receptor subtypes of which only the PD 123319-sensitive one is involved in drinking. But because of the very large doses of PD 123319 used it is also likely that there was loss of receptor specificity resulting in cross-reaction of PD 123319 with AT1 receptors. The results do not favour involvement of AT2 receptors in angiotensin-induced thirst and sodium appetite in the short term.
Cooney
A S
AS
Physiological Laboratory, Cambridge.
Fitzsimons
J T
JT
D000803:Angiotensin I; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001066:Appetite / Q000187:drug effects* / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013777:Tetrazoles / Q000494:pharmacology; D013894:Thirst / Q000187:drug effects* / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D010446:Peptide Fragments; D011725:Pyridines; D011945:Receptors, Angiotensin; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D000803:Angiotensin I; C064745:angiotensin II, 4-amino-Phe(6)-; C118790:angiotensin I (1-7); D019808:Losartan