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. Dopamine D2 receptors are produced in olfactory sensory neurons [Shipley et al. (1991) Chem. Senses 16, 5] and found in relatively high concentrations in their terminals in the nerve and glomerular layers of the olfactory bulb [Nickell et al. (1991) NeuroReport 2, 9-12]. In other systems D2 receptors are linked to adenylyl cyclase by an inhibitory G-protein, and activation of the receptors results in inhibition of the enzyme. 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 bulb. Bromocriptine, a D2 receptor agonist, was added to olfactory epithelium membrane preparations from normal and unilaterally bulbectomized adult rats and the preparations were assayed for forskolin-stimulated adenylyl cyclase activity. In unoperated animals bromocriptine significantly inhibited adenylyl cyclase activity, and the inhibition was abolished following pertussis toxin treatment. In mucosa from unilaterally bulbectomized animals we saw significantly lower adenylyl cyclase activity on the operated side and a further decrease in response to bromocriptine. The data indicate that bromocriptine decreases adenylyl cyclase activity in olfactory tissue, specifically in the sensory neurons, and the reaction is dependent on a pertussis toxin-sensitive G-protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Mania-Farnell
B L
BL
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208-3520.
Farbman
A I
AI
Bruch
R C
RC
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D003714:Denervation; D015259:Dopamine Agents / Q000494:pharmacology*; D004848:Epithelium / Q000201:enzymology; D005260:Female; D008297:Male; D009830:Olfactory Bulb / Q000502:physiology; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D001971:Bromocriptine