title: Hexamethonium-induced augmentation of the electrical twitch response in the guinea-pig ileum longitudinal muscle-myenteric plexus strip.
abstract: Longitudinal muscle-myenteric plexus strips of the guinea-pig ileum were used to investigate the nature of the hexamethonium-induced augmentation of the twitch response. All preparations were set up in Tyrode solution and intermittent longitudinal twitch contractions were evoked by single pulse electrical field stimulation. Hexamethonium, a blocker of nicotinic ganglionic transmission, at 300 μmol/l and 1 mmol/l augmented the twitch contractions by 21% and 35%, respectively. First we tested for a possible nicotinic drive onto an inhibitory neuronal component to the longitudinal smooth muscle cells. However, guanethidine (5 μmol/l), naloxone (1 μmol/l), or l-NAME (300 μmol/l) were without effect on the hexamethonium-induced augmentation. The P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS), 25-100 μmol/l, without altering the control twitch responses, dose-dependently reduced the hexamethonium-induced augmentation; at 100 μmol/l a statistically significantly inhibition was observed. Based on these functional experiments we found no evidence that blocking nicotinic transmission removed a tonic adrenergic, opioidergic or nitrergic inhibitory input to the longitudinal muscle. However, we provide evidence for a hexamethonium-induced augmentation of the P2 purinergic input to cholinergic motoneurons of the guinea-pig ileum longitudinal muscle. The P2-nicotinic receptor interaction presents a novel modulatory mechanism to cholinergic myenteric motor neurons.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University Graz, Universitätsplatz 4, A-8010 Graz, Austria. Electronic address: josef.donnerer@medunigraz.at.
authors.forename: Josef
authors.initials: J
authors.lastname: Donnerer
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University Graz, Universitätsplatz 4, A-8010 Graz, Austria.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Liebmann
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University Graz, Universitätsplatz 4, A-8010 Graz, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzer-Petsche
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology*; D007082:Ileum / Q000294:innervation / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018733:Nicotinic Antagonists; D058919:Purinergic P2 Receptor Antagonists; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D018738:Hexamethonium; D011732:Pyridoxal Phosphate
keywords: Electrical stimulation; Enteric nervous system; Longitudinal muscle–myenteric plexus strip; Nicotinergic input; Purinergic modulation