title: Opposing effects on the phrenic motor pathway attributed to dopamine-D1 and -D3/D2 receptor activation.
abstract: Previous in vivo studies revealed that dopamine-D1-agonists elevate excitability of ventral respiratory column (VRC) neurons and increase discharge activity in the phrenic motor output through actions in the brainstem. In this in vivo study performed on pentobarbital-anesthetized cats, we show that D1-agonists (SKF-38393, dihydrexidine) given intravenously enhanced discharge activity in VRC inspiratory neurons and the phrenic nerve in two stages; discharge intensity first increased to a peak and then discharge duration increased. Cross-correlation analysis of VRC inspiratory neuron and phrenic nerve discharges showed that both stages increased strength of coupling between medullary inspiratory neurons and the phrenic motoneuron output. Intracellular recording and microiontophoresis experiments indicated that D1-agonists produced their stimulatory effects indirectly through actions on synaptic inputs to VRC inspiratory neurons. Because other laboratories have provided evidence that dopamine acting on other types of receptors depresses respiratory neuron excitability we tested the effects of piribedil, an agonist that activates receptors of the generally depressant D3/D2-dopamine receptor family, on phrenic nerve activity. Piribedil depressed phrenic nerve inspiratory discharge intensity, prolonged discharge duration, slowed burst frequency and slowed rate of action potential augmentation. The effects of piribedil were partially counteracted by intravenous injection of dihydrexidine. We propose that under normal, steady state conditions, D1-receptor-mediated excitatory modulation of phrenic motor output overrides D3/D2-receptor mediated inhibition.
authors.affiliation: The University of Wisconsin Medical Sciences Center, United States.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Lalley
authors.forename: Steve W
authors.initials: SW
authors.lastname: Mifflin
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002415:Cats; D018491:Dopamine Agonists / Q000494:pharmacology*; D004525:Efferent Pathways / Q000187:drug effects; D008297:Male; D010617:Phenanthridines / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects*; D010891:Piribedil / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000502:physiology*; D012137:Respiratory System / Q000187:drug effects / Q000294:innervation
chemical_list: D018491:Dopamine Agonists; D010617:Phenanthridines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C061532:dihydrexidine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D010891:Piribedil