Muscarinic cholinergic receptors in area postrema and brainstem areas regulating emesis.

Central cholinergic pathways modulate both the perception of excessive motion stimuli and the expression of motion sickness symptoms, such as nausea and vomiting. Specific brainstem areas which mediate motion-induced emesis include the area postrema (AP), vagal nuclear complex (VNC), reticular formation (RF) at the site of the vomiting center, and the vestibular complex (VC). In this report, histological studies indicated the cellular organization of brainstem structures mediating emesis was similar in bovine and squirrel monkey brain. The objective of this study was to characterize biochemical and pharmacological properties of muscarinic cholinergic receptors assayed by 3H-QNB binding in these regions of bovine brainstem. Scatchard analyses of specific 3H-QNB binding showed an uneven distribution of muscarinic receptors, with high densities of sites in VNC and AP, intermediate levels in RF and lowest receptor concentrations in VC. Dissociation constants for 3H-QNB, measured in saturation and kinetic experiments, were similar in all brainstem regions. The pharmacological potency of cholinergic agonists and antagonists was the same as reported for muscarinic receptors labeled in other brain areas or peripheral organs. Several drugs which potently inhibited 3H-QNB binding in bovine brainstem also exhibited antiemetic activity in a squirrel monkey model of motion-induced emesis. The antimotion sickness effects of these drugs may be due, in part, to their antagonism of muscarinic receptors in brainstem areas regulating emesis.