Receptors for insulin-like growth factors I and II in rat gastrointestinal epithelium.

Distinct receptors for insulin-like growth factors (IGFs) have been characterized in rat intestinal epithelium using 125I-labeled IGF-I and 125I-labeled IGF-II. In jejunal epithelial plasma membranes, IGF-I receptors were observed with a dissociation constant (Kd) of 7.2 nM and a binding capacity of 0.56 pmol/mg protein. Distinct IGF-II receptors were also found with a Kd of 9.5 nM and a binding capacity of 2.61 pmol/mg protein. For IGF-I receptors the following order of affinity was observed: IGF-I greater than IGF-II greater than insulin greater than proinsulin. IGF-II receptors recognize IGF-II with a 20-fold higher affinity than IGF-I and display no cross-reactivity with insulin and proinsulin. Affinity labeling of intestinal membranes also discriminates between the two types of receptors, revealing a radioligand-receptor complex of relative molecular weight (Mr) 130,000 using 125I-IGF-I and 250,000 for 125I-IGF-II under reducing conditions. Separation of proliferative crypt cells from mature villus cells in the small intestine makes it possible to show that a gradient of IGF receptors is present along the crypt-villus axis. 125I-IGF-I and 125I-IGF-II binding is 4.0- and 1.8-fold higher in crypt cells than in villus cells, respectively. Specific 125I-IGF binding is detectable throughout the gastrointestinal tract. The level of IGF binding is similar in stomach, small intestine, and cecum, but higher values are observed in colon.