5-HT1A receptor-mediated inhibition of acetylcholine release from guinea pig myenteric plexus: potential mechanisms.
The mechanisms through which presynaptic 5-HT1A receptors cause inhibition of acetylcholine release from the guinea pig myenteric plexus were investigated. The selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and 5-hydroxytryptamine (5-HT) caused concentration-dependent inhibitions of the electrically evoked release of [3H]acetylcholine from myenteric plexus preparations that had been preincubated with [3H]choline. The inhibitory effects were not modified by the activator of adenylyl cyclase, forskolin (10 microM), the phosphodiesterase inhibitor, AH 21-132 (100 microM), or after pretreatment of the guinea pigs with pertussis toxin (60 micrograms/kg). In contrast, the protein kinase C activator 4 beta- phorbol-12,13-dibutyrate (0.1 microM) prevented the release-inhibiting effect of 8-OH-DPAT, whereas the inactive isomer 4 alpha-phorbol-12,13-dibutyrate (0.1 microM) was without effect. The results suggest that the presynaptic 5-HT1A receptor is not coupled to a pertussis toxin sensitive G protein or to adenylyl cyclase. However, protein kinase C seems to be involved in the mechanism of inhibition of acetylcholine release by presynaptic 5-HT1A receptors.
Dietrich
C
C
Department of Pharmacology, University of Mainz, Germany.
Kilbinger
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D037361:Adenylate Cyclase Toxin; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009197:Myenteric Plexus / Q000378:metabolism*; D009287:Naphthyridines / Q000494:pharmacology; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011985:Receptors, Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D009287:Naphthyridines; D010726:Phosphodiesterase Inhibitors; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; C044843:AH 21-132; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D000109:Acetylcholine