Hypertonic NaCl enhances adenosine release and hormonal cAMP production in mouse thick ascending limb.
Adenosine 3',5'-cyclic monophosphate (cAMP), accumulated in the presence of adenosine, was measured in medullary portions of mouse thick ascending limbs of Henle's loop, suspended either in classic extracellular buffer or in the presence of added NaCl. Under control conditions (140 mmol/l NaCl), adenosine (< 10(-5) mol/l) and N6-cyclohexyladenosine, an A1 adenosine receptor agonist, inhibit the cAMP accumulation induced by arginine vasopressin (AVP). On the other hand, high concentrations of adenosine and CGS-21680, an A2 adenosine receptor agonist, stimulate cAMP formation. Addition of NaCl (+300 mmol/l) to extracellular buffer stimulates the release of endogenous adenosine. It also enhances A2 receptor-induced cAMP accumulation but suppresses A1 receptor-mediated inhibition of adenylyl cyclase. This hypertonic NaCl medium also potentiates the stimulatory action of AVP on adenylyl cyclase. The modifications of tubular responses to both AVP and A1 and A2 agonists, brought about by hypertonic NaCl, were all inhibited by adenosine deaminase, thereby demonstrating the involvement of endogenous adenosine. Adenosine, the release and the effects of which are modulated by hypertonic NaCl, thus appears to act as an endogenous physiological modulator of kidney medulla function.
Baudouin-Legros
M
M
Institut National de la Santé et de la Recherche Médicale Unité 323, Faculté de Médecine Necker-Enfants Malades, Paris, France.
Badou
A
A
Paulais
M
M
Hammet
M
M
Teulon
J
J
D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D006728:Hormones / Q000502:physiology*; D008138:Loop of Henle / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*
D006728:Hormones; D012462:Saline Solution, Hypertonic; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D000241:Adenosine