Role of 5-HT1B/D receptors in canine gastric accommodation: effect of sumatriptan and 5-HT1B/D receptor antagonists.
The 5-HT1B/D receptor agonist sumatriptan has been proposed to treat dyspeptic symptoms, because it facilitates gastric accommodation. It is unknown whether stimulation of 5-HT1B/D receptors is involved. Thus, in four conscious dogs, we compared the effects of sumatriptan alone or combined with N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1-biphenyl]-4-carboxamide hydrocloride (GR-127935), N-[3-[3 (dimethylamino)-ethoxy]-4-methoxyphenyl]-2'-[methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)]-[1,1-biphenyl]-4-carboxamide hydrocloride (SB-216641 hydrochloride), or 3-[4-(4-chloro-phenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol hydrochloride (BRL-15572 hydrochloride) (respectively, nonselective 5-HT1B/D, selective 5-HT1B, and selective 5-HT1D receptor antagonists) on gastric accommodation to isobaric distensions performed with a barostat. An exponential and a linear model were used to fit the pressure-volume relationship. An exponential equation fitted the data better than a linear equation. Sumatriptan (800 nmol/kg iv) induced an immediate gastric relaxation (Deltavolume: 112 +/- 44 ml, P < 0.05). After sumatriptan, the pressure-volume curve was shifted toward significantly higher volumes. This effect was fully reversed by GR-127935 or SB-216641 but not by BRL-15572. In conclusion, 5-HT1B receptors seem to play an important role in modulating gastric accommodation to a distending stimulus. An exponential model for pressure-volume curves fits well with the concept of gastric adaptive relaxation.
De Ponti
Fabrizio
F
Department of Pharmacology, University of Bologna, Via Irnerio 48, I-40126 Bologna, Italy. deponti@biocfarm.unibo.it
Crema
Francesca
F
Moro
Elisabetta
E
Nardelli
Giuseppe
G
Frigo
Gianmario
G
Crema
Antonio
A
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011312:Pressure; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013270:Stomach / Q000294:innervation / Q000502:physiology; D018170:Sumatriptan / Q000494:pharmacology*; D014630:Vagus Nerve / Q000502:physiology
D001549:Benzamides; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; C108531:N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; D010069:Oxadiazoles; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D018723:Bethanechol; C090701:GR 127935; D001285:Atropine; D018170:Sumatriptan; C108532:BRL 15572; D019331:NG-Nitroarginine Methyl Ester