Effects of centrally affecting drugs on the diuretic and antidiuretic actions of intracerebroventricular prostaglandin E2.

Effects of centrally affecting drugs on the diuretic and antidiuretic actions of intracerebroventricularly (i.c.v.) injected prostaglandin (PG) E2 in ethanol-anaesthetized rats were studied. PGE2, when injected i.c.v. at a dose of 1 nmole, produced diuresis followed by antidiuresis. When morphine (0.1 mM) was perfused i.c.v., urine outflow decreased and neither diuretic nor antidiuretic effects of i.c.v. PGE2 was apparent. The perfusions with picrotoxin, gamma-aminobutyric acid and L-glutamate inhibited either the diuretic or the antidiuretic effect of PGE2. On the other hand, when pentobarbital, diazepam, isoniazid and strychnine were perfused i.c.v., the diuretic action of PGE2 was diminished and antidiuresis in response to PGE2 remained unchanged. These results suggested that the diuretic and antidiuretic effects of PGE2 could be separated. The developed of the diuretic effect of PGE2 was completely blocked by amitriptyline and antidiuresis was increased. In rats pretreated i.c.v. with reserpine, the diuretic effect of PGE2 was prolonged and antidiuresis in response to PGE2 was not observed. An antidiuretic action of i.c.v. norepinephrine was not varied by reserpine. Mechanisms for both effects of PGE2 are discussed.