Differential inhibition of cholinergic and noncholinergic neurogenic contractions by 5-hydroxytryptamine1A receptor agonists in guinea pig ileum.
Previous studies have shown that 5-hydroxytryptamine1A (5-HT1A) receptors are localized only to a subset of myenteric neurons in guinea pig ileum; the purpose of this study was to determine the possible functional significance of this differential receptor localization. Nerve-mediated contractions of the longitudinal muscle, myenteric plexus of guinea pig ileum were studied in vitro. Contractions were evoked by single transmural electrical stimuli (0.5-msec duration, at 0.1 Hz; cholinergic) or trains of stimuli (10 or 20 Hz for 1 sec; noncholinergic; scopolamine, 1 microM present). The 5-HT1A agonist, 8-hydroxy-2-(n-dipropylamino)tetralin (DPAT), reduced cholinergic contractions by no more than 14% in the concentration range of 0.001 to 0.3 microM. At high concentrations (1 to 100 microM), DPAT inhibited longitudinal muscle, myenteric plexus contractions; the EC50 was 6 microM. 5-Hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) reduced longitudinal muscle, myenteric plexus contractions by a maximum of 35% and 24% at 100 and 30 microM, respectively. Spiperone and 1-(2-methoxyphenyl)-4-[4-(2-phthalimidobutyl]piperazine (NAN-190), two 5-HT1A receptor antagonists, did not block DPAT-induced inhibition of cholinergic contractions. DPAT (3, 10 and 30 microM) shifted histamine concentration-response curves to the right in an apparently competitive manner; Schild analysis yielded a pA2 of 5.2. DPAT (3, 10, 30 and 100 microM) also shifted bethanechol concentration-response curves to the right in an apparently competitive manner; Schild analysis yielded a pA2 of 5.5. These data indicate that DPAT blocks histamine and muscarinic receptors on longitudinal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
J J
JJ
Galligan
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002794:Choline / Q000502:physiology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology; D006633:Histamine Antagonists / Q000494:pharmacology; D007082:Ileum / Q000294:innervation / Q000648:ultrastructure*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000648:ultrastructure; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001626:Bethanechol Compounds; D006633:Histamine Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D018723:Bethanechol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006632:Histamine; D002794:Choline