Pharmacological and Molecular Characterization of Muscarinic Receptors in Cat Esophageal Smooth Muscle 1

ABSTRACT The muscarinic receptor subtypes that mediate cholinergic responses in cat esophageal smooth muscle were examined. Antagonist effects on carbachol-induced and nerve-evoked contractions were studied in vitro using muscle strips from the distal esophagus. Antagonists displayed similar relative selectivities in suppressing carbachol and nerve-mediated responses as follows: 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) Ͼ zamifenacin Ͼ para-fluoro-hexahydrosiladiphenidol Ͼ pirenzepine Ͼ AF-DX 116 Ͼ methoctramine, indicating that these responses are mediated by the same receptor subtype. 4-DAMP, pirenzepine and methoctramine effects on carbachol responses gave pA 2 values characteristic of the M 3 receptor in both the circular muscle (9.25 Ϯ 0.12, 6.79 Ϯ 0.09 and 6.04 Ϯ 0.11, respectively) and longitudinal muscle (9.46 Ϯ 0.14, 7.25 Ϯ 0.07 and 6.10 Ϯ 0.06, respectively). Reverse transcription-polymerase chain reaction analysis was done using primer sequences based on the cloned human muscarinic receptor subtypes. Messenger RNA for the m 3 receptor was readily identified, whereas m 2 was not detected in esophageal muscle, but was present in cardiac muscle. Sequence homology between the amplified products from cat tissue and the corresponding human m 2 and m 3 receptors genes were 93% and 89%, respectively. In the cat esophagus, the M 3 receptor mediates functional responses and messenger RNA for the corresponding molecular form of this receptor is abundant in this tissue. Muscarinic receptors mediate cholinergic excitation in the distal smooth muscle esophagus. The overall contribution of this excitatory mechanism to normal esophageal peristalsis differs between species. Thus, atropine potently blocks swallow-induced peristalsis in the cat, the monkey and the human esophagus, but in the opossum, it has a more modest effect Five subtypes of the muscarinic receptor (m 1 -m 5 ) have been identified by molecular cloning techniques However, in a recent in vitro study on isolated smooth muscle cells from the circular layer of the cat esophagus

A cost-Utility Analysis Comparing Omeprazole with Ranitidine in the Maintenance Therapy of Peptic Esophageal Stricture

BACKGROUND: Recent studies have suggested that patients receiving omeprazole for prophylaxis against peptic esophageal stricture recurrence have less dysphagia and require fewer repeat dilations than patients receiving ranitidine