Mode of action of calcitonin-gene related peptide in trout gill membranes: evidence for a GTP coupling process.

To evaluate the functional relationship between the calcitonin-gene related peptide (CGRP) receptor in trout gills and guanine nucleotide-binding proteins, we investigated the effect of GTP not only on the CGRP stimulated adenylate cyclase activity but also on the human CGRP binding to trout gill membranes. In the presence of 1 microM GTP, the basal and the CGRP stimulated adenylate cyclase activity were increased by 1.8-fold. In addition, GTP decreased the CGRP binding to gill membranes and accelerated the dissociation of bound labeled hormone. Scatchard analysis of the data revealed that the reduction of human CGRP binding by GTP was mainly due to a decrease in the binding affinity with no significant change in the binding capacity. Thus, the binding of CGRP to fish gill membranes activates adenylate cyclase via a guanine nucleotide dependent mechanism, suggesting the involvement of a guanine nucleotide-binding stimulatory protein in the action of CGRP in fishes.