Antidiuretic effects of dibutyryl-cyclic AMP microinjected into the hypothalamic supraoptic nucleus in water-loaded...

Effects of dibutyryl-cyclic AMP (db-cAMP) and cyclic AMP (cAMP) microinjected into the hypothalamic supraoptic nucleus (SON) which contains the neurons synthesizing and releasing antidiuretic hormone upon the outflow and the osmotic pressure of urine and the other visceral functions were investigated in water-loaded rats anesthetized with ethanol. When microinjected into the SON the dibutyryl analog of cAMP induced dose-dependent antidiuretic effects without significant effects on any other visceral functions. Dibutyryl-cAMP was much more effective than cAMP; The ED50 value for db-cAMP was approx. 200 nmol versus more than 500 nmol for cAMP. The time course of the antidiuretic effects was relatively slow with minimal urine outflow appearing only after more than 1/2 hour post-injection. The effects induced by db-cAMP demonstrated tachyphylaxis and were partially inhibited by pretreatment with atropine or theophylline, which suggests that the antidiuretic effects were mediated through muscarinic and adenosine receptors present in the nucleus.