Response of the human cardia sphincter to circulating prostaglandins F2ALPHA and E2 and to antiinflammatory drugs.

Abstract

SUMMARY The effects on intraluminal pressure in the oesophagus, the cardiac sphincter, and the gastric fundus of intravenous prostaglandin F2a, E2, and of rectal indomethacin were studied in 41 subjects. Intravenous infusion of prostaglandin F2a (005 to 0-8 ,tg kg-' min-') produced marked, dose-related and sustained elevation of cardiac sphincter pressure without significantly affecting oesophageal peristalsis or gastric fundal motility. Sphincteric relaxation during swallowing was prolonged. Plasma gastrin levels were unchanged. Intravenous infusion of PGE2 (0-08 ,tg kg-' min-') inhibited sphincter contractions to serial bolus intravenous injections of pentagastrin (0.1 or 0-2 ,ug kg-'). Rectal indomethacin (200 mg) resulted in a rise of cardiac sphincter pressure, suggesting that endogenous synthesis of an inhibitory (E-type) prostaglandin was suppressed. The results indicate that prostaglandin E2 may be concerned in the regulation of cardiac sphincter tone in man, whilst prostaglandin F2a may be useful in the treatment of gastrooesophageal reflux.Pressure level in the cardiac sphincter plays a part in the prevention of gastrooesophageal reflux and depends upon the tone of circular oesophageal muscle in that area. The neural and humoral control of sphincteric tone is not completely understood. Human alimentary muscle is highly sensitive to prostaglandins (PGs): in vitro PGE2 produces relaxations and PGF2, contractions of the circular muscle layer (Bennett, Murray, and Wyllie, 1968;Bennett, Eley, and Scholes, 1968;Bennett and Posner, 1971). Prostaglandin E2 occurs naturally in the human gastric mucosa (Bennett, Stamford, and Unger, 1972). We have recorded motor responses of the human gastrooesophageal junction to intravenous PGF2a and PGE2. The effects on cardiac sphincteric pressure of rectally administered indomethacin have also been studied. Methods and SubjectsIntraluminal pressures were measured with a four-'Present address: The Middlesex Hospital, London 2Present address: Mount Sinai Hospital,

Estimation and Characterization of Prostaglandins in the Human Gastrointestinal Tract

“…The responsiveness of gastrointestinal muscle to prostaglandin E and F compounds is well known (Bennett & Fleshler, 1970 Dilawari, Newman, Poleo & Misiewicz (1975) suggest that prostaglandin E2 may be involved in both the physiology and pathophysiology of the human lower oesophageal sphincter.…”

The Contribution of Prostaglandins in the Muscle of Human Isolated Small Intestine to Neurogenic Responses

“…Studies employing inhibitors of prostaglandin action or synthesis indicate that in isolated intestine, prostaglandins contribute to the regulation of muscle tone and rhythmic activity (Bennett & Posner, 1971;Eckenfels & Vane, 1972;Ferreira, Herman & Vane, 1972;1976;Botting & Salzmann, 1974;Willis, Davison & Ramwell, 1974;Bennett, Eley & Stockley, 1975a;Burleigh, 1977). In vivo, prostaglandin E2 may help control human cardiac sphincter tone (Dilawari, Newman, Poleo & Misiewicz, 1975).…”

Lower Esophageal Sphincter and Acupuncture: Electromanometric Evaluation in Esophageal Achalasia

“…(2) LES is known to have many receptors for neurohumoral factors [15], Prostaglandins E|, Ey and A cause a fall in LES tone with a myogenic effect, but this action is not modified by vagotomy [ 16], The same decrease has also been observed with enkephalins in vitro [17]. In opossum, serotonin causes LES relaxation with excita tion of inhibitory myenteric neurones [18].…”