Demonstration of adrenergic and dopaminergic receptors in cultured sympathetic neurons--their coupling to cAMP but not to the transmitter release process.
Experiments were carried out on cultured sympathetic neurons of the chick embryo; first, to demonstrate the presence of adrenergic and dopaminergic receptors, and then to see if these receptors are involved in regulation of transmitter release. We show that alpha 2-agonists, norepinephrine, epinephrine and clonidine, had no effect on neuronal cyclic 3',5'-adenosine monophosphate content. Forskolin enhanced neuronal cyclic 3',5'-adenosine monophosphate from a control value of about 20 pmoles/mg protein to 150 pmoles/mg protein. In the presence of alpha 2-agonists and forskolin the cyclic 3,5'-adenosine monophosphate content increased between 340 and 430 pmoles/mg protein. The alpha 1-agonist, phenylephrine, had no such effect. The facilitatory effect of alpha 2-agonist on forskolin-stimulated cyclic 3',5'-adenosine monophosphate production was blocked by the alpha 2-antagonist, yohimbine, but not the alpha 1-agonist, prazosin. Dopamine did not affect neuronal cyclic 3',5'-adenosine monophosphate content, but forskolin-stimulated increase in cyclic 3',5'-adenosine monophosphate was further facilitated by dopamine, and this effect was blocked by haloperidol. Activation of neuronal alpha 2-receptors by norepinephrine, epinephrine and clonidine did not interfere with electrically induced release of tritium from [3H]-norepinephrine-loaded sympathetic neurons. However, if sympathetic neurons were co-cultured with heart cells, clonidine, norepinephrine and epinephrine markedly inhibited the stimulation-induced release. Yohimbine or phentolamine partially reversed the inhibitory effects of alpha 2-agonists. alpha 2-Agonists and -antagonists also modified stimulation-induced release of tritium from [3H]norepinephrine-loaded hearts of the chick embryo.(ABSTRACT TRUNCATED AT 250 WORDS)
Wakade
A R
AR
Department of Pharmacology, State University of New York, Brooklyn 11203.
Wakade
T D
TD
Bhave
S V
SV
Malhotra
R K
RK
D000320:Adrenergic Fibers / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009638:Norepinephrine / Q000493:pharmacokinetics*; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D005576:Colforsin; D000242:Cyclic AMP; D009638:Norepinephrine