Effect of dopamine receptor agonists on sensory nerve activity: possible therapeutic targets for the treatment of asthma and COPD.
Sensory nerves regulate central and local reflexes such as airway plasma leakage, and cough and their function may be enhanced during inflammation. Evidence suggests that dopamine receptor agonists may inhibit sensory nerve-mediated responses. In this study dopamine inhibited vagal sensory nerve induced microvascular leakage in the rat. In order to characterize the receptor involved rat vagus preparations were utilized. Quinagolide (D(2/3) agonist), ropinirole (D(2/3/4) agonist), SKF 38393 (D(1/5) agonist), AR-C68397AA (Viozan) (dual D(2)/B(2) agonist) and dopamine inhibited hypertonic saline induced depolarization by approximately 50%. Data suggests that AR-C68397AA and quinagolide also inhibited depolarization of the human vagus. The quinagolide response was blocked by sulpiride (D(2/3) antagonist) but not SCH 23390 (D(1/5) antagonist); ropinirole was partially blocked by sulpiride, totally blocked by spiperone (at a concentration that blocks all dopamine receptors) but not by SCH 23390. The response to SKF 38393 was not blocked by sulpiride but was by SCH 23390. The inhibition evoked by AR-C68397AA was only partially blocked by SCH 23390 but not by sulpiride or spiperone whereas dopamine was blocked by spiperone. The effect of dopamine was not stimulus-specific as it inhibited capsaicin-induced depolarization of the rat vagus in a spiperone sensitive manner. In conclusion, dopamine receptor ligands inhibit depolarization of the rat and human vagus. These data suggest that dopamine receptor agonists may be of therapeutic benefit in the treatment of symptoms such as cough and mucus secretion which are evident in respiratory diseases such as asthma and chronic obstructive pulmonary disease.
Birrell
Mark A
MA
Department of Cardiothoracic Surgery, Respiratory Pharmacology Group, Faculty of Medicine, The National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY.
Crispino
Natascia
N
Hele
David J
DJ
Patel
Hema J
HJ
Yacoub
Magdi H
MH
Barnes
Peter J
PJ
Belvisi
Maria G
MG
D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D002199:Capillary Permeability; D002211:Capsaicin / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D014132:Trachea / Q000098:blood supply / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D012462:Saline Solution, Hypertonic; D013134:Spiperone; D002211:Capsaicin; D004298:Dopamine