The mechanisms underlying heart stimulation by dopamine, with special reference to direct and indirect beta adrenoceptor stimulation.
1. The positive chronotropic and norepinephrine-releasing effects of dopamine were examined in the isolated guinea pig heart, using the Langendorff model. 2. The released norepinephrine was estimated from the norepinephrine concentration measured in the post-perfusion solution using HPLC. 3. The dose-response curve for dopamine to stimulate the heart rate (HR) closely resembled that for the norepinephrine release. A selective beta 1 antagonist bisoprolol completely abolished the positive chronotropic effect, but did not affect the norepinephrine release. 4. The HR increase in response to 3 mumol/L dopamine was 54 +/- 15% (n = 14) of the control in normal hearts. The response was decreased to 15 +/- 7% (n = 6) by pretreatment with reserpine. 5. A D1 antagonist, SKF83742, (3 mumol/L) shifted the dose-response curve for the dopamine-induced norepinephrine release toward the right, indicating the involvement of D1-like dopamine receptors. 6. Voltage clamp experiments using single cells isolated from the right atrium revealed that dopamine is a weak partial agonist for beta adrenoceptors. Dopamine stimulated the L-type Ca2+ current with a threshold concentration of 3 mumol/L. 7. These findings indicate the important role of the norepinephrine release in the stimulation of beta adrenoceptors by dopamine at clinically relevant concentrations.
Habuchi
Y
Y
Department of Clinical Laboratory and Medicine, Kyoto Prefectural University of Medicine, Japan.
Tanaka
H
H
Yamamoto
T
T
Komori
T
T
Nishio
M
M
Yoshimura
M
M
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D017298:Bisoprolol / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D018492:Dopamine Antagonists; D011943:Receptors, Adrenergic, beta; D017447:Receptors, Dopamine D1; C035674:SK&F 83742; D012110:Reserpine; D004298:Dopamine; D009638:Norepinephrine; D017298:Bisoprolol