STIMULATION OF THE ADENYLYL-CYCLASE ACTIVITY IN HUMAN ENDOMETRIAL MEMBRANES BY VIP AND RELATED PEPTIDES

Vasoactive intestinal peptide (VIP) has been shown to stimulate adenyl yl cyclase activity in human endometrial membranes. The effect was dep endent on the time and temperature of incubation as well as on the con centration of endometrial membrane proteins in the medium. In the pres ence of 1 muM GTP, half-maximal stimulation of adenylyl cyclase activi ty was observed at 25.0 +/- 7.0 nM VIP, whereas the maximal activity ( at 1 muM VIP) corresponded to an increase of about 140% with respect t o basal values (7.5 +/- 0.6 pmol cyclic AMP/min/mg of protein). Howeve r, the maximal stimulation of adenylyl cyclase activity was obtained w ith helodermin (1 muM) that increased the activity by 170% over the ba sal. The relative potency of VIP-related peptides upon the adenylyl cy clase activity was: helodermin (ED50 = 1.8 +/- 1.4 nM) > VIP(ED50 = 25 .0 +/- 7.0 nM) > PHI (ED50 = 725.0 +/- 127.2 nM). Secretin had a faint effect upon the adenylyl cyclase activity and glucagon was completely inefficient at this level. The presence of alpha(s) and alpha(i) subu nits of G proteins in human endometrium was detected by immunoblot. Pr eliminary results showed the presence of two classes of I-125-VIP rece ptors in human endometrial membranes with the following stoichoimetric parameters: high affinity receptor (Kd = 2.0 nM, binding capacity 0.1 pmol VIP/mg protein) and low affinity receptor (Kd = 0.43 muM, bindin g capacity 13.1 pmol VIP/mg protein). The present results together wit h the known presence of VIP in human uterus and the actions of this ne uropeptide in the adjacent myometrial tissue support the idea that VIP and related peptides may have a role in human endometrium.