Evidence for angiotensin II receptors in the urinary bladder of the rabbit.
Dose-response (DR) curves for several angiotensin analogs were examined on isolated rabbit detrusor strips with washout and rest between each addition. The order of potency was [Val5]-angiotensin II greater than [Ile5]-angiotensin II greater than [Ile5]-angiotensin I greater than [Val4]-angiotensin III. Repeated cumulative DR to [Val5]-AII resulted in a gradual increase in potency and intrinsic activity for four DR. However, the maximum force generated occurred at lower agonist concentrations and was less than that of the single methods, suggesting tachyphylaxis. Atropine (1.0 microM) shifted the cumulative DR curve downward, suggesting some cholinergic component possibly involving a presynaptic site of action. The magnitude of field-stimulated atropine-resistant contractions was reduced by both 1.0 and 10 microM saralasin as well as 10 microM naloxone. Tissue binding with 125I-labelled angiotensin II on isolated detrusor smooth muscle membranes indicated specific binding saturation occurred at 14.3 fmol/mg with a KD of 0.72 nM in EDTA-Tris buffered saline. Thus our results show that angiotensin II (AII) receptors can be demonstrated in destrusor muscle by ligand binding experiments on cell membranes and that saralasin and naloxone partially block atropine-resistant contractions. However, it seems unlikely that AII serves as a neurotransmitter because of the delay in onset of action of exogenous AII in isolated bath experiments and the apparent inability of saralasin to totally abolish the atropine-resistant field-stimulated preparation. If AII serves a role in neurotransmission it most probably is as a neuromodulator.
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008566:Membranes / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012504:Saralasin / Q000494:pharmacology; D001743:Urinary Bladder / Q000378:metabolism*
D007457:Iodine Radioisotopes; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D001285:Atropine; D012504:Saralasin