Serotonin and GABA-induced depolarizations of frog primary afferent fibers.
The interaction of gamma-aminobutyric acid (GABA) and serotonin (5-HT) on primary afferent terminals of the isolated frog spinal cord was investigated by sucrose gap recordings from dorsal roots. Application of 5-HT (1.0-100 microM) to the Ringer's solution significantly reduced afferent terminal depolarizations elicited by concentrations of GABA ranging from 0.1 to 1.0 mM. The reductions of GABA-depolarizations which were produced by 1.0 microM 5-HT were mimicked by the 5-HT1A agonists 8-OH-DPAT (8-hydroxy-2-(n-dipropylamino)tetralin) and ipsapirone. The effects of ipsapirone were reversed by the 5-HT1A antagonist spiperone. The decreases of GABA-depolarizations produced by high doses of 5-HT were duplicated by application of alpha-methyl-5-HT, a 5-HT1C/2 agonist and reversed by superfusion of the cord with manserin, a 5-HT1C/2 antagonist. The presumptive 5-HT1A receptor-mediated effects of 1.0 microM 5-HT and 8-OH-DPAT appeared to result from a direct action on afferent terminals because the reduction of GABA responses was unchanged by addition of TTX to the Ringer's solution. In contrast, the putative 5-HT1C/2 receptor actions of 100 microM 5-HT and alpha-methyl-5-HT were substantially reduced by TTX and are presumably caused by activation of receptors located on interneurons. GABAB receptors did not appear to be affected by addition of 5-HT at low or high concentrations because baclofen-induced afferent terminal hyperpolarizations remained unchanged during exposure to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
Gharagozloo
A
A
Department of Neurology, University of Miami School of Medicine, FL 33101.
Holohean
A M
AM
Hackman
J C
JC
Davidoff
R A
RA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000344:Afferent Pathways / Q000187:drug effects*; D000818:Animals; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D011894:Rana pipiens; D011963:Receptors, GABA-A / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011743:Pyrimidines; D011963:Receptors, GABA-A; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C042390:alpha-methylserotonin; D012701:Serotonin; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin