Effect of anti‐inflammatory drugs on the binding of calcium to cellular membranes in various human and guinea‐pig tissues

Abstract

Summary1. Cellular membranes were obtained by centrifugation of homogenates of various human and guinea-pig tissues. These membranes took up added calcium (Ca) when incubated at 250 C for 10 min in histidine buffer at pH 7-4. The uptake of Ca was increased by the presence of adenosine triphosphate (ATP).2. Evidence is presented that the membrane fragments which took up Ca under these conditions were derived from the endoplasmic reticulum. 3. The ATP-dependent uptake of Ca by membranes derived from guinea-pig aortic or gastric smooth muscle or from human umbilical arterial muscle was inhibited by indomethacin in a concentration-dependent manner. 4. The ATP-dependent uptake of Ca by membranes derived from heart, brain, skeletal muscle or liver of the guinea-pig was not inhibited by indomethacin. 5. Endothelial cells were obtained from the lining of the human umbilical vein. Cellular membranes were prepared from the endothelial cells by homogenization and centrifugation. The endothelial membranes took up added Ca in the presence of added ATP and this uptake was inhibited by indomethacin and also by members of a group of pharmacologically-related drugs.

Antagonism of Prostanoid‐induced Contractions of Rat Gastric Fundus Muscle by Sc‐19220, Sodium Meclofenamate, Indomethacin or Trimethoquinol

“…These results with PGE1 are similar to those in which the f-adrenoceptor stimulant, isoxsuprine (0.1 to 1 jg/ml) reduced the fundic contraction to PGE, without greatly affecting the response to ACh (Coceani & Wolfe, 1966 produced only weak selective inhibition of contractions to PGEr so making the tendency for a differential effect on PGE, and PGE2 difficult to detect (Lacey & Sanger, 1980 . There are also regional differences in prostanoid receptor type or distribution in the circular muscle of guinea-pig ileum and colon (Bennett & Sanger, 1978; (Northover, 1973), and papaverine-like activity with high concentrations of trimethoquinol (see Hanna & Eyre, 1979). The extent to which blockade of contractions is due to interaction with various prostanoid receptors is therefore not known, but it seems likely that rat gastric fundus contains a multiplicity of prostanoid receptor types.…”

The Inhibition of Histamine Release From Rat Peritoneal Mast Cells by Non‐steroid Anti‐inflammatory Drugs and Its Reversal by Calcium

“…The entry of calcium into the mast cell is known to be an important stage in the release process (Foreman et al, 1973) and certain 'anti-allergic' drugs, such as disodium cromoglycate, which inhibit histamine release, may act by preventing this calcium movement (Foreman, Mongar, Gomperts & Garland, 1975). It is therefore pertinent that several aspirin-like drugs have been shown to interfere with the uptake and binding of calcium in various tissues (Northover, 1973). Thus, inhibition of histamine release, following challenge with a variety of agents, by the non-steroid anti-inflammatory drugs in vitro could reflect actions on calcium influx into the mast cell.…”

Role of Prostaglandins and Arachidonic Acid Derivatives in the Coupling of Cerebral Blood Flow to Cerebral Metabolism

“…Inhibition of this en zyme in the brain would be predicted to produce cerebral vasodilatation both by a direct vascular smooth muscle effect and secondarily via stimula tion of cerebral metabolism. Indomethacin has ef fects on various ionic fluxes in molluscan neurones and various human and guinea-pig tissues but only at concentrations of 0.5-1 mM (Northover, 1973 ;Levitan and Barker, 1972). The direction of these membrane phenomena, when applied to the in vivo situation, would predict that indomethacin would provoke vasodilatation, not vasoconstriction.…”