BROMOCRIPTINE, A DOPAMINE D2 RECEPTOR AGONIST, INHIBITS ADENYLYL-CYCLASE ACTIVITY IN RAT OLFACTORY EPITHELIUM

The presence of large numbers of dopaminergic neurons in the olfactory bulb suggests that dopamine plays an important role in olfaction. Dop amine D2 receptors are produced in olfactory sensory neurons [Shipley et al. (1991) Chem. Senses 16, 5] and found in relatively high concent rations in their terminals in the nerve and glomerular layers of the o lfactory bulb [Nickell et al. (1991) NeuroReport 2, 9-12]. In other sy stems D2 receptors are linked to adenylyl cyclase by an inhibitory G-p rotein, and activation of the receptors results in inhibition of the e nzyme. We examined rat olfactory mucous membrane to determine whether the D2 receptors were linked functionally to adenylyl cyclase as they are in other tissues. Adenylyl cyclase is found in both the olfactory cilia of the sensory epithelium and olfactory nerve terminals in the b ulb. Bromocriptine, a D2 receptor agonist, was added to olfactory epit helium membrane preparations from normal and unilaterally bulbectomize d adult rats and the preparations were assayed for forskolin-stimulate d adenylyl cyclase activity. In unoperated animals bromocriptine signi ficantly inhibited adenylyl cyclase activity, and the inhibition was a bolished following pertussis toxin treatment. In mucosa from unilatera lly bulbectomized animals we saw significantly lower adenylyl cyclase activity on the operated side and a further decrease in response to br omocriptine. The data indicate that bromocriptine decreases adenylyl c yclase activity in olfactory tissue, specifically in the sensory neuro ns, and the reaction is dependent on a pertussis toxin-sensitive G-pro tein. Given the absence of dopaminergic input to the olfactory epithel ium, we propose that dopamine D2 receptors are more probably functiona lly linked to the adenylyl cyclase that is being transported to the ax on terminals than to the adenylyl cyclase in cilia. The results also s uggest that receptors are coupled to G-proteins before they are transp orted to nerve terminals.