Opioidergic and dopaminergic modulation of respiration.
Opioids, dopamine and their receptors are present in many regions of the bulbar respiratory network. The physiological importance of endogenous opioids to respiratory control has not been explicitly demonstrated. Nonetheless, studies of opioidergic respiratory mechanisms are important because synthetic opiate drugs have respiratory side effects that in some situations pose health risks and limit their therapeutic usefulness. They can depress breathing depth and rate, blunt respiratory responsiveness to CO2 and hypoxia, increase upper airway resistance and reduce pulmonary compliance. The opiate respiratory disturbances are mainly due to agonist activation of mu- and delta-subtypes of receptor and involve specific types of respiratory-related neurons in the ventrolateral medulla and the dorsolateral pons. Endogenous dopaminergic modulation in the CNS and carotid bodies enhances CO2-dependent respiratory drive and depresses hypoxic drive. In the CNS, synthetic agonists with selectivity for D1-and D4-types of receptor slow respiratory rhythm, whereas D2-selective agonists modulate acute and chronic responses to hypoxia. D1-receptor agonists also act centrally to increase respiratory responsiveness to CO2, and counteract opiate blunting of CO2-dependent respiratory drive and depression of breathing. Cellular targets and intracellular mechanisms responsible for opioidergic and dopaminergic respiratory effects for the most part remain to be determined.
Lalley
Peter M
PM
Department of Physiology, The University of Wisconsin School of Medicine and Public Health, Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA. pmlalley@facstaff.wisc.edu
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism*
D000701:Analgesics, Opioid; D004298:Dopamine