sincalide and Vomiting

Total parenteral nutrition (TPN) induces biliary dilatation, sludge and formation of gallstones. Cholecystokinin (CCK) induces gallbladder (GB) contraction. During thyrotropin-releasing hormone (TRH) testing for thyroid function, we observed that patients felt a strong micturition reflex attributable to smooth muscle contraction of the bladder. The possibility of GB contraction after TRH administration was studied compared to cholecystokinin-octapeptide (CCK-OP) and/or fatty meal administration. The effect of intravenous (IV) CCK-OP, TRH and a combination of the two on GB volume was studied in normal volunteers without GB or liver disease and in patients receiving TPN for greater than 2 weeks. Subjects included six normal volunteers who received an oral fatty meal only, 18 other normal volunteers (Group A) and 18 TPN patients (Group B). Gallbladder contraction was estimated by ultrasound prior to and after administration of the fatty meal; in the other 36 subjects, GB contraction was calculated prior to and after administration of CCK-OP, TRH, or both. Results are expressed as a percentage of the GB basal volume using each subject as his or her own control. Group A and Group B were each divided into three equal subgroups receiving IV CCK-OP (A1, B1), TRH (A2, B2), or both (A3, B3).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Colic; Dietary Fats; Female; Gallbladder; Heartburn; Humans; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Nausea; Parenteral Nutrition, Total; Sincalide; Sodium Chloride; Thyrotropin-Releasing Hormone; Urination; Vomiting

The gastrointestinal motor correlates of vomiting consist of two contractile events, 1) a giant retrogradely propagated contraction of the upper small intestine, the retrograde giant contraction (RGC) and 2) a series of post-RGC phasic contractions that occur primarily in the lower small intestine. The effects of cholinergic, dopaminergic, serotonergic, and opioid receptor antagonists and an opioid receptor agonist on vomiting and its gastrointestinal motor correlates initiated by apomorphine (APO), CuSO4, or cholecystokinin octapeptide (CCK-8) were determined in awake dogs. Atropine blocked the retrograde giant contraction only, and hexamethonium blocked all jejunoileal motor responses activated by APO, CuSO4, or CCK-8. Domperidone blocked all effects of APO only, whereas haloperidol, methysergide, 1-(1-naphthyl) piperazine, and fentanyl blocked or inhibited responses to both APO and CuSO4. None of the dopaminergic, serotonergic, or opioid receptor antagonists or the opioid receptor agonist affected the gastrointestinal motor responses to CCK-8. Cinanserin or Sch 23390 had no effect on any of the responses activated by APO, CuSO4, or CCK-8. These results suggested that D2 dopaminergic and 5-HT2 serotonergic receptors of the emetic central pattern generator mediate vomiting and its gastrointestinal motor correlates, whereas opioid receptors may mediate tonic inhibition of these responses. In addition, peripheral muscarinic or nicotinic cholinergic receptors but not peripheral 5-HT2, dopaminergic, or opioid receptors mediate the gastrointestinal motor correlates of vomiting.

Topics: Animals; Apomorphine; Atropine; Copper; Copper Sulfate; Digestive System; Dogs; Domperidone; Female; Gastrointestinal Motility; Haloperidol; Hexamethonium; Hexamethonium Compounds; Male; Muscle Contraction; Naloxone; Receptors, Cholinergic; Receptors, Dopamine; Receptors, Neurotransmitter; Receptors, Opioid; Receptors, Serotonin; Serotonin Antagonists; Sincalide; Vomiting

The gastrointestinal motor and myoelectric responses associated with vomiting induced by apomorphine (APO) and activated by cholecystokinin octapeptide (CCK-8) were compared as well as the mechanisms of initiation of these responses. Twelve dogs were surgically implanted with strain-gauge force transducers or bipolar electrodes for chronic recording of contractile or electrical activity. The responses to CCK-8 were determined in the fasted state and compared with the gastrointestinal motor and myoelectric correlates of vomiting activated by APO. After recording control responses, the effects of the following agents on these responses were determined: atropine, domperidone, and proglumide. In addition, the effects of supradiaphragmatic vagotomy or splanchnicectomy were determined. We found that CCK-8 activated contractile and myoelectric responses in the absence of vomiting, which were similar in most respects to those found in association with vomiting. These responses included 1) the retrograde giant contraction (RGC) and 2) the post-RGC phasic contractions. These RGCs were similar with respect to their activation in an all-or-none fashion, magnitude, duration, and position in the small intestine. The myoelectric correlates of these motor responses were similar qualitatively and quantitatively. The responses activated by APO and CCK-8 differed with respect to their coordination at different levels of the gastrointestinal tract. Whether activated by CCK-8 or APO, atropine blocked the RGC but not the post-RGC contractions. Domperidone blocked all responses to APO but not to CCK-8, and splanchnicectomy did not affect responses to either agent. Vagotomy blocked all gastrointestinal responses to APO but not to CCK-8. These results indicated that CCK-8 activates the gastrointestinal motor and myoelectric correlates of vomiting by a peripheral mechanism that does not include dopamine receptors.

Topics: Animals; Apomorphine; Denervation; Digestive System; Digestive System Physiological Phenomena; Dogs; Electrophysiology; Female; Male; Peristalsis; Sincalide; Splanchnic Nerves; Vagotomy; Vomiting