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 the extracellular domain of the type 1 angiotensin II receptor (AT1), we demonstrated the presence of angiotensin II (AII) receptors in human fallopian tube. Immunoperoxidase staining for AT1 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 ovarian cycle and weakest after menopause. Ligand binding assay confirmed that the AII receptor concentration was highest in the mucosa of fallopian tubes from premenopausal women. Mucosa from the ampullary segment had higher concentrations of AII receptor than the fimbrial and isthmic segments in both premenopausal and postmenopausal women. Displacement studies using specific AII receptor subtype antagonists showed that approximately 60% of the total activity could be displaced by CGP42112B (type 2 specific) and 40% by losartan (AT1 specific). Immunoblotting confirmed that the antibody detected a protein of approximately 60 kDa. Functional studies showed that AII had a stimulatory action on tubal ciliary beat frequency, but had no significant effect on myosalpingseal activity. This effect was achieved at nanomolar concentrations of AII; further increases in the AII concentration were without additional effect. The stimulatory effect of AII was inhibited by the specific AT1 antagonist losartan, whereas the type 2 antagonist, CGP42112B, had no effect. The data demonstrate that AII may play an important role in ovum transport and fertility.
Saridogan
E
E
Academic Department of Obstetrics, Gynecology, and Reproductive Physiology, London Hospital Medical College, Whitechapel, United Kingdom.
Djahanbakhch
O
O
Puddefoot
J R
JR
Demetroulis
C
C
Collingwood
K
K
Mehta
J G
JG
Vinson
G P
GP
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000378:metabolism / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects* / Q000502:physiology*; D005187:Fallopian Tubes / Q000737:chemistry / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D019808:Losartan; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D011247:Pregnancy; D017697:Premenopause; D011945:Receptors, Angiotensin / Q000032:analysis / Q000502:physiology*; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology; D014018:Tissue Distribution
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; D019808:Losartan