Guanine nucleotides and pertussis toxin reduce the affinity of histamine H3 receptors on AtT-20 cells

Abstract

Agonist occupancy of high affinity histamine H₃ receptors on AtT-20 cells induces increased ACTH release. However, the signal transduction process by which this occurs is presently unknown. As a first step in characterizing this pathway, we have examined the effects of a variety of nucleotides and nucleotide analogs on N^a-methylhistamine binding to these receptors. Nonhydrolyzable guanine nucleotide analogs inhibit up to 40% of the [³H]N^a-methylhistamine binding by increasing the dissociation rate of the ligand from the receptor and thereby, reducing receptor affinity. Pertussis toxin also decreases the affinity of the H₃ receptors and ADP ribosylates a 41 kDa protein. Neither GTPγS nor pertussis toxin changeB _max. These data indicate that the H₃ receptors on these cells are coupled to a G protein of the G_i subclass.