Comparison of human and porcine gastric clasp and sling fiber contraction by M2 and M3 muscarinic receptors.
To compare the gastroesophageal junction of the human with the pig, M(2) and M(3) receptor densities and the potencies of M(2) and M(3) muscarinic receptor subtype selective antagonists were determined in gastric clasp and sling smooth muscle fibers. Total muscarinic and M(2) receptors are higher in pig than human clasp and sling fibers. M(3) receptors are higher in human compared with pig sling fibers but lower in human compared with pig clasp fibers. Clasp fibers have fewer M(3) receptors than sling fibers in both humans and pigs. Similar to human clasp fibers, pig clasp fibers contract significantly less than pig sling fibers. Analysis of the methoctramine Schild plot suggests that M(2) receptors are involved in mediating contraction in pig clasp and sling fibers. Darifenacin potency suggests that M(3) receptors mediate contraction in pig sling fibers and that M(2) and M(3) receptors mediate contraction in pig clasp fibers. Taken together, the data suggest that both M(2) and M(3) muscarinic receptors mediate the contraction in both pig clasp and sling fibers similar to human clasp and sling fibers.
Vegesna
Anil K
AK
Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Braverman
Alan S
AS
Miller
Larry S
LS
Tallarida
Ronald J
RJ
Tiwana
Mansoor I
MI
Khayyam
Umar
U
Ruggieri
Michael R
MR
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004943:Esophagogastric Junction / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034421:Sus scrofa
D001572:Benzofurans; D003959:Diamines; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D002217:Carbachol; C101207:darifenacin; C054938:methoctramine