Correlation between myometrial receptor affinity, lipophilicity and antagonistic potency of oxytocin analogues in the rat.
Purified myometrial plasma membrane fractions were prepared from rats treated with oestradiol to induce oestrus. The binding affinities of 11 antagonistic oxytocin analogues to the oxytocin receptor of the plasma membranes were measured. Furthermore, lipophilicity of the peptides was assessed by reversed-phase high pressure liquid chromatography. No significant correlation was found between lipophilicity of the analogues and values for antagonistic potencies or binding affinities. Also, receptor-binding affinity did not correlate with in-vitro antagonistic activity whereas a significant correlation was obtained between binding affinities and in-vivo antagonistic potency for analogues void of partial agonist properties. It is concluded that neither receptor affinity nor lipophilicity in the analogues can predict the potency of the antagonists in vitro. However, receptor affinity was found to be a relatively good predictor of the in-vivo potency, while the usefulness of measuring antagonistic potency in vitro is questioned.
Atke
A
A
Department of Medical Physiology C, Panum Institute, University of Copenhagen, Denmark.
Vilhardt
H
H
Melin
P
P
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D009215:Myometrium / Q000378:metabolism*; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism*; D018045:Receptors, Oxytocin
D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D010121:Oxytocin