Short Communications the Action of Dibutyryl Cyclic Gmp (n²-2' O-dibutyryl Cyclic Guanosine-3', 5'-mono - Phosphate) on the Ileum of Guinea Pig

It has been recently indicated that relaxation of the guinea-pig taenia by Q-adrenergic stimulants or papaverine is associated with increased concentration of cyclic AMP (cyclic adenosine-3', 5'-monophosphate) in the cells (1-5). On the other hand cyclic GMP (cyclic guanosine-3', 5'-monophosphate) is present in considerable amounts in various mammalian tissues, particularly in the gastrointestinal tract (6). Furthermore, in adipose tissue, cyclic GMP and cyclic AMP were found to act in opposite directions (7). These findings led to investigation of the mode of action of dibutyryl-cyclic GMP on guinea pig ileum. A piece of the ileum from the male guinea pig (300 to 350 g in body wt.) was suspended in 10 ml organ bath. Responses of the ileum to drugs were recorded through an isotonic lever. Locke Ringer solution gassed with a mixture of 95 % 0, and 5 % CO, and kept at 32°C was used as a bath fluid. Locke Ringer solution contained NaCI 9.0 g, KCI 0.4 g, CaCl, 0.2 g, MgCl, 0.2 g, NaHCO3 0.5 g and glucose 0.5 g in a litre. In some experiments NaCI and NaHCO, of Locke Ringer solution were replaced by KCI and KHCO3. This modified Locke Ringer solution has been termed K-Locke Ringer solution in this paper. The results in this paper are presented as the mean of ten experiments. Dibutyryl cyclic GMP slowly contracts the ileum in a dose-response relationship. In two out of ten preparations, contraction produced by dibutyryl cyclic GMP (10-a g/ml) was partly inhibited by tetrodotoxin (3 X 10' g/ml) and atropine (10-6 g/ml). In the other eight preparations tetrodotoxin (3 ;' 10' g/ml) or atropine (10-e g/ml) had little influence on the action of dibutyryl cyclic GMP (10' g/ml), though atropine (10' g/ml) completely inhibited the contractions produced by nicotine and acetylcholine while tetrodotoxin abo lished that by nicotine (Fig. IA). The ileum which was suspended in K-Locke Ringer solution for 60 min was used as a K-depolarized ileum. The actions of acetylcholine and BaCl2 were greatly reduced by depolarization of the membrane. On the other hand, dibutyryl cyclic GMP in a con centration of 5 x 10-5 g/ml clearly contracted the K-depolarized ileum, though no response