Baclofen inhibits ANP-mediated cyclic GMP synthesis in the rat cervical spinal cord.
The neurotransmitter gamma-aminobuteric acid (GABA) is believed to have a controlling action on spinal locomotor networks. In spasticity, spinal locomotor networks are thought to play a role. A well known drug in the treatment of spasticity is the GABA(B) agonist Baclofen. We report an inhibitory effect of Baclofen on the ANP-mediated cGMP synthesis in the superficial dorsal horn (laminae I-III) of the rat cervical spinal cord. This inhibitory effect of Baclofen could not be detected after incubation with the NO donor SNP. The clinical effect of Baclofen on the reduction of spasticity might be explained by an enhancement of GABAergic inhibition of ANP mediated cGMP concentration in the spinal cord dorsal horn, thus reducing afferent input.
de Louw
A J A
AJ
Department of Neurology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. adl@sneu.azm.nl
de Vente
J
J
Steinbusch
H P J
HP
Steinbusch
H W M
HW
Troost
J
J
Vles
J S H
JS
D000375:Aging / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001418:Baclofen / Q000494:pharmacology*; D002574:Cervical Vertebrae; D006152:Cyclic GMP / Q000096:biosynthesis*; D018755:GABA Agonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D007150:Immunohistochemistry; D008297:Male; D009128:Muscle Spasticity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009415:Nerve Net / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018080:Receptors, GABA-B / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D020030:Nitric Oxide Donors; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D001418:Baclofen