High concentrations of dopamine and epinephrine protect dopaminergic D2 receptors from inactivation by phenoxybenzamine on primary cultured rat lactotrophs.
The effect of a high concentration of catecholamines on phenoxybenzamine pretreatment was examined. The efficacy of the pretreatments was monitored by testing the inhibitory action of dopamine on prolactin release. Phenoxybenzamine is a beta-haloalkylamine which alkylates and irreversibly inactivates adrenergic alpha-receptors in smooth muscle. Dopaminergic D2 receptors share several common characteristics with the alpha-receptors. Primary cultured male rat pituitary cells were used. After phenoxybenzamine (0.1 mumol/l) pretreatment, the inhibitory action of dopamine on prolactin release was significantly reduced in a perifusion system. When the cells were pretreated with phenoxybenzamine in medium containing 0.1 or 1 mmol/l dopamine, the 0.1-mmol/l dopamine did not change the effect of phenoxybenzamine on inactivation of the receptors, but the 1-mmol/l dopamine eliminated the effect of phenoxybenzamine pretreatment. These observations were confirmed with a static monolayer culture system. The observations illustrate that a high concentration of dopamine forms a D2 receptor-dopamine complex and protects the D2 from inactivation by phenoxybenzamine. When the cells were pretreated with 0.1 mumol/l phenoxybenzamine in a medium containing 1 mmol/l epinephrine, the effect of the phenoxybenzamine was also eliminated, suggesting that a sufficient amount of D2 receptor-epinephrine complex was formed to protect the receptor from inactivation. The hormone release in response to a secretagogue depends on its affinity and intrinsic activity. It is, therefore, suggested that the intrinsic activity of epinephrine is much lower than that of dopamine on prolactin release, since the D2 receptor-epinephrine complex is as stable as the D2 receptor-dopamine complex, and the inhibitory action of epinephrine on prolactin release is less than 10% of that of dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Shin
S H
SH
Department of Physiology, Queen's University, Kingston, Canada.
Heisler
R L
RL
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism*; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism
D017448:Receptors, Dopamine D2; D010643:Phenoxybenzamine; D011388:Prolactin; D004298:Dopamine; D004837:Epinephrine