HYPERTONIC NACL ENHANCES ADENOSINE RELEASE AND HORMONAL CAMP PRODUCTION IN MOUSE THICK ASCENDING LIMB

Adenosine 3',5'-cyclic monophosphate (cAMP), accumulated in the presen ce of adenosine, was measured in medullary portions of mouse thick asc ending limbs of Henle's loop, suspended either in classic extracellula r buffer or in the presence of added NaCl. Under control conditions (1 40 mmol/l Nacl), adenosine (< 10(-5) mol l/l) and N-6-cyclohexyladenos ine, an A(1) adenosine receptor agonist, inhibit the cAMP accumulation induced by arginine vasopressin (AVP). On the other hand, high concen trations of adenosine and CGS-21680, an A(2) adenosine receptor agonis t, stimulate cAMP formation. Addition of NaCl (+300 mmol/l) to extrace llular buffer stimulates the release of endogenous adenosine. It also enhances A(2) receptor-induced cAMP accumulation but suppresses A(1) r eceptor-mediated inhibition of adenylyl cyclase. This hypertonic NaCl medium also potentiates the stimulatory action of AVP on adenylyl cycl ase. The modifications of tubular responses to both AVP and A(1) and A (2) agonists, brought about by hypertonic NaCl, were all inhibited by adenosine deaminase, thereby demonstrating the involvement of endogeno us adenosine. Adenosine, the release and the effects of which are modu lated by hypertonic NaCl, thus appears to act as an endogenous physiol ogical modulator of kidney medulla function.