Angiotensin II receptors in the rat urinary bladder smooth muscle: type 1 subtype receptors mediate contractile responses.
Angiotensin II (Ang II) receptors in the rat urinary bladder smooth muscle were investigated by in vitro responses of smooth muscle strips to exogenous Ang II stimulation and in radioligand binding assays. Ang II (10(-10) M. to 10(-5) M.) caused a potent contractile response in a concentration-dependent manner. Using the recently developed nonpeptide subtype-selective antagonists, the Ang II-induced contractile response was further characterized. The Ang II-induced contractile response was inhibited weakly by the type 2 subtype (AT2)-selective antagonist PD123319 but was potently inhibited by the type 1 subtype (AT1)-selective antagonist DuP 753 with a pA2 value of 9.03, suggesting that the response is mediated predominantly by AT1 receptors. [125I]Ang II was used to specifically label a single class of binding sites with a dissociation constant of 0.31 nM. and a maximal binding capacity of 41.5 fmol./mg. of protein. DuP 753 could completely antagonize the binding of Ang II in a particulate fraction of rat bladder (Ki = 14 nM), whereas PD123319 did not have any effect in the concentration range of 10(-9) to 10(-5) M. The results suggest that AT1 receptors rather than AT2 receptors predominantly mediate Ang II-induced contraction in the rat urinary bladder.
Tanabe
N
N
Department of Urology, Yamanashi Medical College, Japan.
Ueno
A
A
Tsujimoto
G
G
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan