The inhibition of ganglionic transmission via presynaptic dopamine DA1 and postsynaptic DA2 receptor activation in the canine cardiac sympathetic ganglia.
The involvement of dopaminergic mechanisms in modulating ganglionic transmission of the dog cardiac sympathetic ganglia were investigated in both in vivo and in vitro experiments. The positive chronotropic responses to preganglionic stellate stimulation were inhibited by R(+)SK&F38393 and talipexole administered directly to the ganglia through the artery, and the inhibitory effects were antagonized by pretreatment with R(+)SCH23390 and S(-)sulpiride, respectively. McN-A-343 and 1,1-dimethyl-4-phenylpiperazinium iodide given through the artery to reach the ganglia displayed dose-dependent positive chronotropic effects. The positive chronotropic effects were inhibited by (-)quinpirole and talipexole, but not by R(+)SK&F38393. The inhibitions were antagonized by S(-)sulpiride and tended to be antagonized by yohimbine. The acetylcholine output from the isolated stellate ganglia by preganglionic stimulation (5 Hz) was unaffected in the presence of (-)quinpirole and talipexole, but was concentration-dependently reduced in the presence of R(+)SK&F38393, and the reduction was antagonized by R(+)SCH23390. The results thus suggest that the dopamine receptor agonists inhibit the ganglionic transmission by reducting acetylcholine release via preganglionic DA1 receptor stimulation and by inhibiting postganglionic nicotinic and muscarinic activation via postganglionic DA2 receptor stimulation.
Mukai
M
M
Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
Kushiku
K
K
Yamada
H
H
Yamada
K
K
Dan
K
K
Furukawa
T
T
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004285:Dogs; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D001381:Azepines; D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004246:Dimethylphenylpiperazinium Iodide; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C024763:talipexole; D013469:Sulpiride; D000109:Acetylcholine