Effects of Cholinergic Drugs and Imidazole on Ca Release and Cyclic AMP Formation in Microsomal Fractions from Rabbit Colon

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Abstract
Following the addition of carbachol or acetylcholine to microsomal fractions isolated from rabbit colon which were preloaded with Ca, the ions were rapidly released. In the 35-45% fraction Ca was completely released within 10 min, but in the 35% fraction only 30% was released. Carbachol reduced the adenylate cyclase activity of the 35-45% fraction. Both these effects were blocked by atropine. Exogenous cyclic AMP completely inhibited the Ca-releasing action of carbachol in the 35% fraction and markedly reduced it in the 35-45% fraction. Imidazole released Ca from the 35-45% fraction and stimulated its phosphodiesterase activity. The microsomal fractions were probably parts of a Ca-sequestering system in smooth muscle which were able to bind Ca, and which on the addition of some contracting drugs released the ions and thereby activated the contractile system. The release of Ca may have been at least partly due to a reduction of the adenylate cyclase activity, although other mechanisms must also be considered.