ANGIOTENSIN-II RECEPTORS AND ANGIOTENSIN-II STIMULATION OF CILIARY ACTIVITY IN HUMAN FALLOPIAN-TUBE

Using an antibody (6313/G2) directed against a specific sequence in th e extracellular domain of the type 1 angiotensin II receptor (AT(1)), we demonstrated the presence of angiotensin II (AII) receptors in huma n fallopian tube. Immunoperoxidase staining for AT(1) receptor showed positive staining in the epithelium of the tubal mucosa. The intensity of staining varied depending upon the hormonal status at the time of salpingectomy, being strongest in the proliferative phase of the ovari an cycle and weakest after menopause. Ligand binding assay confirmed t hat the AII receptor concentration was highest in the mucosa of fallop ian tubes from premenopausal women. Mucosa from the ampullary segment had higher concentrations of AII receptor than the fimbrial and isthmi c segments in both premenopausal and postmenopausal women. Displacemen t studies using specific AII receptor subtype antagonists showed that approximately 60% of the total activity could be displaced by CGP42112 B (type 2 specific) and 40% by losartan (AT(1) specific). Immunoblotti ng confirmed that the antibody detected a protein of approximately 60 kDa. Functional studies showed that AII had a stimulatory action on tu bal ciliary beat frequency, but had no significant effect on myosalpin geal activity. This effect was achieved at nanomolar concentrations of AII; further increases in the AII concentration were without addition al effect. The stimulatory effect of AII was inhibited by the specific AT(1) antagonist losartan, whereas the type 2 antagonist, CGP42112B, had no effect. The data demonstrate that AII may play an important rol e in ovum transport and fertility.