Loperamide: novel effects on capacitative calcium influx.
Loperamide is a widely used antidiarrheal that primarily acts at nanomolar concentrations through activation of opioid receptors in the gastrointestinal tract. At somewhat higher concentrations, loperamide blocks calmodulin activity, calcium channels, N-methyl-D-aspartate-receptor channels, and maitotoxin-elicited calcium influx. Loperamide at micromolar concentrations has now been shown to have a remarkable stimulatory effect on the capacitative calcium influx that is triggered in many cells by depletion of the inositol-trisphosphate-sensitive stores of calcium in the endoplasmic reticulum. The mechanism whereby loperamide enhances levels of intracellular calcium elevated by capacitative calcium influx is, as yet, undefined.
Daly
J W
JW
Laboratory of Bioorganic Chemistry, National Institutes of Health Bethesda, Maryland 20892, USA. johnd@intra.niddk.nih.gov
Harper
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000930:Antidiarrheals / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004064:Digestive System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004553:Electric Conductivity; D006801:Humans; D008139:Loperamide / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D000930:Antidiarrheals; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008139:Loperamide; D000255:Adenosine Triphosphate; D002118:Calcium