Brainstem Dopamine Controls Gastric Tone And Motility

Abstract

Gastrointestinal (GI) dysfunctions, such as gastroparesis, are prodromic to Parkinson's disease (PD). Upper GI functions are modulated by neurons in the dorsal vagal complex (DVC); recently, we reported a monosynaptic dopaminergic connection between the substantia nigra pars compacta (SNpc) and the DVC, activation of which modulates gastric tone and motility via dopamine (DA)1 receptors. The effects of DVC application of DA on gastric tone and motility, however, have not been characterized.Gastric tone & motility were recorded in rats using strain gauges sewn onto the anterior gastric wall. DA (0.1pmoles‐10nmoles/60nL; N=10‐16) microinjected in the left DVC decreased tone & motility in both the corpus (at 1nmole, tone: ‐152±21mg; motility: ‐57±6% of baseline) and in the antrum (at 1nmole, tone: ‐222±22 mg; motility: ‐41±6% of baseline, respectively; P<0.05 for all).Equivalent doses of DA induced a larger decrease in antrum compared to corpus tone, while motility was affected similarly. The effects of DA were blocked by ipsilateral vagotomy (N=4) and by application of DA2 (L741626), but not DA1 (SCH23390), antagonists (both at 45nM, N=7).DVC application of the dopamine uptake inhibitor, benztropine (100nmoles, N=2‐6), decreased tone (‐76±24 and ‐245±85mg) but increased motility (23±7 and 41±18% of baseline) in corpus and antrum, respectively.Our data indicate that the dopaminergic innervation of the DVC modulates gastric tone and motility differentially: when exogenous DA is applied, the effects are mediated mainly via DA2 receptors, which are also tonically active in setting gastric tone; conversely, a tonic DA1 input modulates gastric motility. We would like to suggest that this latter pathway is involved in the reduced gastric motility observed in PD.