Dopamine receptor 1 modulates the discharge activities of inspiratory and biphasic expiratory neurons via cAMP-dependent pathways.

Dopamine receptor 1 (D(1)R) plays an essential role in regulating respiratory activity in mammals, however, little is known about how this receptor acts to modulate the basic respiratory rhythmogenesis. Here, by simultaneously recording the discharge activities of biphasic expiratory (biphasic E) neurons/inspiratory (I) neurons and the XII nerve rootlets from brainstem slices, we found that the application of D(1)R agonist cis-(±)-1-(aminomethyl)-3,4-dihydro-3-phenyl-1H-2-benzopyran-5,6-diolhydrochloride (A68930, 5 μM), or forskolin, an intracellular cAMP-increasing agent, substantially decreased respiratory cycle and expiratory time of both types of neurons, and elevated the integral amplitude and frequency of XII nerve rootlets discharge. These changes were reversed by subsequent application of their antagonists SCH-23390 and Rp-Adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt hydrate (Rp-cAMPS), respectively. Importantly, after pretreatment with Rp-cAMPS, the effects of A68930 in both types of neurons were blocked, suggestive of a cAMP-dependent action of A68930. Thus, the current study indicates that D(1)R may modulate basic breathing rhythmogenesis via cAMP-dependent mechanisms.