sigma2 Site-mediated inhibition of electrically evoked guinea pig ileum longitudinal muscle/myenteric plexus contractions.
Functional and binding studies were performed in order to characterize the relative efficacy and affinity of a number of compounds that bind to sigma sites. The ability of sigma site ligands to inhibit electrically evoked contraction of the guinea pig ileum longitudinal muscle/myenteric plexus preparation was compared to the affinities of these compounds for sigma1 sites (assessed by displacement of [3H](+)-pentazocine) and sigma2 sites (assessed by displacement of [3H]1,3-di-o-tolylguanidine (DTG) in the presence of 5 microM dextromethorphan). It was shown that the rank order of potencies for suppression of electrically evoked contractions of guinea pig ileum perfectly matched the rank order of affinities of these compounds for the sigma2 binding site, while correlating poorly with the sigma1 binding site. In addition, no significant correlations were found between the efficacy of the tested compounds to inhibit contraction of the guinea pig ileum preparation and previously reported affinities for muscarinic, dopamine D2 or MK-801 binding sites. Thus, the present study represents the first functional bioassay selectively sensitive to agents interacting with the sigma2 receptor subtype binding site, and provides a means with which to further elucidate the functional role of sigma2 sites.
Kinney
G G
GG
Astra Arcus USA, Department of Biology, Rochester, NY 14602, USA. KINNEY_G@FISONS.COM
Harris
E W
EW
Ray
R
R
Hudzik
T J
TJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology*; D017480:Receptors, sigma / Q000187:drug effects / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology
D017480:Receptors, sigma; D013469:Sulpiride