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)
Galligan
J J
JJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
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