title: Methiothepin attenuates gastric secretion and motility effects of vagal stimulants at the dorsal vagal complex.
abstract: Methiothepin, a nonselective 5-HT receptor antagonist was utilized to explore the 5-HT modulation of dorsal vagal complex-TRH (thyrotropin releasing hormone) analogue stimulated gastric functional parameters. Intracisternal methiothepin pretreatment (200, 0.1 nmol) produced significant inhibition (70%, 44%, respectively) of the TRH analogue [p-Glu-His-(3,3'-dimethyl)-Pro NH2; RX 77368 (12 pmol)]-induced gastric acid output compared to vehicle pretreatment. Intracisternal pretreatment with methysergide (nonspecific 5-HT receptor antagonist) or combined cyanopindolol (5-HT(1A and 1B) receptor antagonist)+ritanserin (receptor antagonist of the 5-HT(2) family) did not alter the dorsal vagal complex-RX 77368 response. Unilateral dorsal vagal complex pretreatment with methiothepin (50 nmol/50 nl) attenuated ipsilateral dorsal vagal complex-TRH analog (12 pmol) induced gastric secretory response by 57%. The gastric secretagogue response to stimulation of the raphe obscurus (mediated by TRH release into the dorsal vagal complex) was inhibited 50% by pretreatment with intracisternal dorsal medullary methiothepin (0.1 nmol/10 microl). Intracisternal methiothepin (200 nmol/20 microl) also attenuated (a) dorsal vagal complex-glutamate (60 nmol/30 nl) stimulated gastric acid secretion and (b) gastric motility stimulated by dorsal vagal complex-RX 77368 (12 pmol/30 nl). The data suggest that other properties of methiothepin, alone or in addition to its 5-HT receptor antagonist effect, mediate its inhibitory actions at the dorsal vagal complex.
authors.affiliation: 304 Hamilton Hall, 1645 Neil Avenue, Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Varanasi
authors.forename: Jinhan
authors.initials: J
authors.lastname: Chi
authors.forename: Robert L
authors.initials: RL
authors.lastname: Stephens
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D018698:Glutamic Acid / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology*; D008784:Methysergide / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D012702:Serotonin Antagonists; D016713:Ritanserin; D018698:Glutamic Acid; C047975:cyanopindolol; D008719:Methiothepin; D010869:Pindolol; D007608:Kainic Acid; D008784:Methysergide