Document Detail

D1/D2-dopamine receptor agonist dihydrexidine stimulates inspiratory motor output and depresses medullary expiratory neurons.
MedLine Citation:
PMID:  19279296     Owner:  NLM     Status:  MEDLINE    
It is now accepted that dopamine plays an important neuromodulatory role in the central nervous control of respiration. D1, D2, and D4 subtypes of the receptor seem to be important players, but the assignment of various respiratory tasks to specific subtypes of the dopamine receptor is a work in progress. In the present investigation, dihydrexidine (DHD), a full dopamine receptor agonist with affinity for both D1- and D2-subtypes of receptor, was tested for its effects on inspiratory neurons and motor output and on membrane potential properties of medullary bulbospinal expiratory augmenting expiratory neurons in the pentobarbital anesthetized adult cat. The effects of DHD were compared with those of the highly selective D1-dopamine receptor (D1R) agonists SKF-38393 and 6-chloro-APB. DHD increased the intensity and duration of inspiratory motor output. Phrenic nerve discharge intensity was increased and prolonged, contributing to elevated inspiratory effort and duration when spontaneous breathing was monitored with tracheal pressure measurements. Intracellular recording from rostral medullary inspiratory neurons revealed that DHD, like SKF-38393, increases and prolongs inspiratory phase membrane depolarization, resulting in a longer and more intense discharge of action potentials. Remarkably, DHD had opposite effects on Aug-E neurons. Membrane potential was hyperpolarized, and action potential discharges were suppressed or abolished. In association with reduction of discharge intensity, action potential half width was reduced and after-hyperpolarization increased. The stimulatory action of DHD on inspiratory motor output is attributed to D1R effects, while the depression of Aug-E neurons seems to be linked to D2R actions on the postsynaptic membrane.
Peter M Lalley
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-11
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  296     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-21     Completed Date:  2009-07-02     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1829-36     Citation Subset:  IM    
Department of Physiology, The University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
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MeSH Terms
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
Action Potentials
Benzazepines / pharmacology
Dopamine Agonists / pharmacology*
Exhalation / drug effects*
Inhalation / drug effects*
Motor Neurons / drug effects*,  metabolism
Neural Inhibition / drug effects
Phenanthridines / pharmacology*
Phrenic Nerve / drug effects,  metabolism
Receptors, Dopamine D1 / agonists*,  metabolism
Receptors, Dopamine D2 / agonists*,  metabolism
Respiratory Center / drug effects*,  metabolism
Respiratory Muscles / innervation*
Synaptic Transmission / drug effects
Time Factors
Grant Support
Reg. No./Substance:
0/Benzazepines; 0/Dopamine Agonists; 0/Phenanthridines; 0/Receptors, Dopamine D1; 0/Receptors, Dopamine D2; 32D64VH037/dihydrexidine; 67287-49-4/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 80751-65-1/SK&F 82958

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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