Clearance of oxytocin and its potentially enzyme resistant analogues in the OXT-receptor compartment of the potassium depolarized rat myometrium.

The time-response behaviour of a group of oxytocin analogues structurally modified on potential sites of oxytocin splitting by tissue inactivation enzymes ("enzyme probes") was investigated ex vivo on the potassium depolarized rat myometrium (at 30°C) and compared with the data obtained in the in vivo experiments. The modified oil-immersion method by Kalsner and Nickerson was used to record time profiles after cessation of a steady state myometrium contraction triggered by analogues in a high potassium tissue medium. An exchange of the aqueous medium for mineral oil enables to suppress return diffusion of the peptide and to record its irreversible clearance near the corresponding receptor compartment.

Kinetics of oxytocin and deaminooxytocin displacement from the OXTR-receptor compartment in rat uterus ex vivo.

The oil immersion method suggested earlier by Kalsner and Nickerson for analysing actions of sympathomimetic drugs upon smooth muscle tissues was applied to isometric preparations of rat myometrium stimulated by oxytocin and deaminooxytocin. An exchange of the aqueous medium by mineral oil allows monitoring the displacement of the peptides from their receptor compartment in absence of free diffusion transport between tissue and organ medium. Exponential analysis of the data from the uterotonic decay phase allows several inferences to be drawn: 1) Transport rate constants (roughly equal for the two peptides) are higher than rate constants of (irreversible) elimination from the receptor compartment.

Thermodynamics of the interaction between oxytocin and its myometrial receptor in sheep: a stepwise binding mechanism.

Entropy (ΔS), enthalpy (ΔH) and heat capacity (ΔCp) changes attending the oxytocin interaction with its two binding sites on myometrial cell membranes in sheep were derived from the temperature dependence of Kd values. The high affinity oxytocin site (Kd on the order of 10(-9)mol l(-1), 25 °C), ascribed to the oxytocin receptor (OXTR), is entropy-driven in the temperature range 0-37 °C. Enthalpy component prevails as a driving force in the binding to the low affinity site (Kd ≈ 10(-7)) within the higher temperature range.

Thermodynamic descriptors, profiles and driving forces in membrane receptor-ligand interactions.

Extension of the (isothermal) Gibbs-Helmholtz equation for the heat capacity terms (ΔC(p)) allows formulating a temperature function of the free (Gibbs) energy change (ΔG). An approximation of the virtually unknown ΔC(p) temperature function enables then to determine and numerically solve temperature functions of thermodynamic parameters ΔH and ΔS (enthalpy and entropy change, respectively). Analytical solutions and respective numeric procedures for several such approximation formulas are suggested in the presented paper.

Uterine contractile response to the graded infusion of oxytocin in guinea pigs near term.

Objective: Myometrial oxytocin binding characteristics do not change near term in guinea pigs. We tested the hypothesis that the uterine contractile response to oxytocin does not change near term.

Study Design: Chronically instrumented guinea pigs were given graded infusions of oxytocin (n = 19 animals) or saline solution (n = 4 animals) on days 58, 60, and 62 and then daily until delivery (term, 68 days).