Characterization of the interaction between gastrin and its receptor in rat oxyntic gland mucosa

A gastrin receptor, identified in crude membrane preparations of rat oxyntic gland mucosa, has an equilibrium dissociation constant (Kd) of approx. 4 . 10(-10)M and a binding capacity of 4 fmol/mg protein. The binding capacity was significantly lower after 2 days of fasting, parallel with a significant drop in serum gastrin levels; there was no change in Kd. In order to verify Scatchard analysis and to determine if there was a coincident alteration in the association (k+1) and dissociation (k-1) rates in the fasted rat, a kinetics study was performed. Under our conditions, there appeared to be a single set of binding sites and the binding reaction obeyed first-order dissociation, and second-order association rate kinetics. Second-order association rate kinetics were validated by demonstrating the independence of the rate constants when there were alterations in the concentrations of reactants. The average k+1 was determined to be 2 . 10(6) M-1 . s-1. The average k-1 was determined to be 1 . 10(-3) s-1. There was no significant change in the k+1 and k-1 in fed and fasted rats. Fasting decreased the number of gastrin receptors without altering the affinity of the receptor for the hormone.