D1 receptors play a major role in the dopamine modulation of mouse ileum contractility.
Since the role of dopamine in the bowel motility is far from being clear, our aim was to analyse pharmacologically the effects of dopamine on mouse ileum contractility. Contractile activity of mouse ileum was examined in vitro as changes in isometric tension. Dopamine caused a concentration-dependent reduction of the spontaneous contraction amplitude of ileal muscle up to their complete disappearance. SCH-23390, D1 receptor antagonist, which per se increased basal tone and amplitude of spontaneous contractions, antagonized the responses to dopamine, whilst sulpiride or domperidone, D2 receptor antagonists, were without effects. The application of both D1 and D2 antagonists had additive effects. SKF-38393, D1 receptor agonist, mimicked dopamine-induced effects. Dopamine responses were insensitive to tetrodotoxin, atropine, nitric oxide synthase inhibitor or adenosine receptor antagonists, but they were reduced by adenylyl cyclase inhibition or apamin. Dopamine at a concentration which did not cause a significant reduction of phasic contractions inhibited the cholinergic contractions in response to field stimulation. SCH-23390 per se induced an increase of the neural cholinergic contraction and antagonized the dopamine effects, whilst sulpiride or domperidone did not. The application of D1 and D2 antagonists had additive effects. In conclusion, mouse ileum is under basal inhibitory control by dopamine, through D1 receptor activation, linked to adenylyl cyclase and activation of apamin-sensitive potassium channels. An agonistic interaction of the dopamine receptor subtypes in the regulation intestinal contractility has being also highlighted. This study would provide new insight on the pharmacology of the modulation of the gastrointestinal contractility by dopamine.
Dipartimento di Biologia Cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, Viale delle Scienze, I-90128 Palermo, Università di Palermo, Italy.
Maria Grazia
MG
Zizzo
Flavia
F
Mulè
Mariangela
M
Mastropaolo
Rosa
R
Serio
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D017615:Enteric Nervous System / Q000502:physiology; D007082:Ileum / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D015221:Potassium Channels; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D000262:Adenylyl Cyclases; D004298:Dopamine