抄録
This study was attempted to clarify the mechanism of antidiuretic action of chlorpropamide and its related substances, such as tolbutamide, carbutamide, acetohexamide, phenylurea, phenylhydroxyurea, phenylmethylurea, phenyldimethylurea, acetanilide, acetophenetidine, acetaminophen, aminopyrine, phenylbutazone, oxyphenbutazone; by using the urinary bladder of toads, Bufo vulgaris japonicus, which showed a good response to vasopressin and cyclic 3', 5'-AMP.
6.8×10-3M chlorpropamide and carbutamide added to the serosal solution resulted in an increase in net water flux even in the absence of vasopressin. Other analgetics and urea related compounds also induced an increase in water permeability. The effect of these substances on water permeability was inhibited by 10-5M epinephrine on the serosal side and that of vasopressin was also inhibited but not exogenous cyclic 3', 5'-AMP. These substance even in a lower concentration also intensified the action of vasopressin on water permeability. In contrast, sulfanilamide, urea, methylurea, dimethylhydroxyurea and benzylurea showed no effect on water permeability under the above experimental conditions.
The action of cyclic 3', 5'-AMP on water permeability was interfered with by 5×10-3M chlorpropamide and 1.4×10-3M oxyphenbutazone in the presence of 10-5M epinephrine on the serosal solution, while 1.4×10-3M phenylmethylurea, acetaminophen, acetanilide, and aminopyrine resulted in a slight increase in the response to cyclic 3', 5'-AMP.
The effect of 6.8×10-3M chlorpropamide and 2mU/ml vasopressin on water permeability was inhibited by addition of 10-2M Ca++ or 10-2M glutathione to the serosal solution, but not the effect of 10-3M cyclic 3', 5'-AMP.
The substances, in which the increase in water permeability was observed, resulted in the decrease in potential difference and short-circuit current and in the decrease in electrical conductance calculated by SCC/P. D.
The above results may suggest that chlorpropamide and oxyphenbutazone inhibit leaking of intrinisic cyclic 3', 5'-AMP through the serosal membrane and induce elevation of intracellular concentration of cyclic AMP, but the mechanism of the action of other substances which induce an increase in water permeability is not clear at present.
