The effect of vasoactive intestinal peptide (VIP) on the contractile activity of human uterine smooth muscle.
1. In the present study we examined the in vitro effect of vasoactive intestinal peptide (VIP) on spontaneous contractions in both inner and outer layers of non-pregnant human myometrium. A dose-dependent relaxation was observed, but with a marked difference in sensitivity to VIP between the two layers, with an IC50 value of 1 x 10(-8) and 1 x 10(-5) mol L in the outer and inner layers, respectively. 2. We also established that VIP did not directly stimulate the adenylate cyclase activity. The only slight stimulations were observed in non-initial rate conditions. The maximal response of this indirect effect was obtained for VIP concentrations between 1 x 10(-9) and 1 x 10(-8) mol/L and this occurred to the same extent (an approximately 1.4-fold increase) in both layers. However this response is specific, since structurally related peptides such as glucagon, gastric inhibitory polypeptide (GIP), secretin, or human growth hormone-releasing factor (hGRF) had no effect in our preparations. 3. Autoradiographic studies revealed that specific VIP binding sites were located on the vascularization of the intermediate vascular layer and on arterioles and venules distributed in the inner and outer myometrial layers. They were also present in the endometrium, but not on smooth muscle cells of either layer. 4. Such observations could provide evidence for another signal transduction pathway to mediate the biological effect of VIP. An additional intermediate step on the vascularization distributed in all of the muscle cannot be excluded.
Leroy
M J
MJ
INSERM, U.166, Maternité Baudelocque, Paris, France.
Tanguy
G
G
Vial
M
M
Rostène
W
W
Malassiné
A
A
Ferré
F
F
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D001345:Autoradiography; D001665:Binding Sites; D000242:Cyclic AMP / Q000096:biosynthesis; D004717:Endometrium / Q000098:blood supply / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D013268:Stimulation, Chemical; D014590:Uterine Contraction / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases