Dopaminergic D2 receptors activate PKA to inhibit spinal pelvic-urethra reflex in rats.
To clarify the role of descending dopaminergic innervation in reflexive urethral closure, the impacts of dopaminergic D2 receptor (DR2)-selective agonists and antagonists on repetitive stimulation-induced pelvic-to-urethra spinal reflex potentiation (SRP) were tested using in vivo rat preparations. Pelvic afferent nerve test stimulation (TS; 1 pulse/30 s for 30 min) evoked baseline reflex activity with single spikes in the external urethral sphincter electromyogram (EUSE), whereas, repetitive stimulation (RS; 1 pulse/s for 30 min) induced SRP. Intrathecal application of quinelorane dihydrochloride (Q110; 10, 30, and 100 nM, 10 microl, a selective DR2 agonist) dose dependently inhibited the RS-induced SRP. Pretreatment with L135 (100 nM, 10 microL it, a selective DR2 antagonist) antagonized the Q110-dependent inhibition (100 nM, 10 microl it). Intrathecal AMPA (10 microM, 10 microl, a selective glutamatergic AMPA receptor agonist), and NMDA (10 microM, 10 microl, a selective glutamatergic NMDA receptor agonist) reversed the Q110-dependent inhibition. Intrathecal forskolin (100 nM, 10 microl, a PKA activator) prevented the Q110-dependent inhibition that was reversed by CNQX (10 microM, 10 microl it, a selective glutamate AMPA receptor antagonist) and APV (10 microM, 10 microl it , a selective glutamate NMDA receptor antagonist). Our results suggest that DR2 activation, which inactivates intracellular PKA, may be involved in descending dopaminergic inhibition of NMDA/AMPA receptor-dependent SRP at the lumbosacral spinal cord, which is thought to be involved in reflexive urethral closure.
Wu
Hsi-Chin
HC
China Medical University Hospital, China Medical University, Taichung, Taiwan.
Chiu
Chun-Hsien
CH
Tung
Kwong-Chung
KC
Chen
Gin-Den
GD
Peng
Hsien-Yu
HY
Lin
Tzer-Bin
TB
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D004576:Electromyography; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D023421:Models, Animal; D016202:N-Methylaspartate / Q000494:pharmacology; D010388:Pelvis / Q000294:innervation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D014521:Urethra / Q000294:innervation / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D065127:Dopamine D2 Receptor Antagonists; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D017868:Cyclic AMP-Dependent Protein Kinases