OPPOSITE ROLES OF CAMP AND CGMP ON VOLUME LOSS IN MUSCLE-CELLS

It is controversial whether changes in adenosine 3',5'-cyclic monophos phate (cAMP) and in the cAMP-to-guanosine 3',5'-cyclic monophosphate ( cGMP) ratio are involved with cell swelling and in the activation of v olume-regulatory mechanisms. We examined whether these nucleotides are involved in cell volume regulation in skeletal muscle. Isolated (inta ct and internally perfused) barnacle muscle cells were used because th ese cells, when exposed to a hyposmotic environment, undergo an extrac ellular Ca2+ (Ca-o)-dependent regulatory volume decrease (RVD). Using intact cells we found that dibutyryl cAMP and forskolin significantly promoted RVD in cells exposed to Ca-o-free solutions and that dibutyry l cGMP significantly inhibited RVD in cells exposed to Ca-o-containing solutions. In perfused cells in which the intracellular free Ca2+ con centration ([Ca2+](i)) was heavily buffered [with 8 mM ethylene glycol -bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)], cAMP i nduced a volume loss that was inhibited by presence of cGMP. Furthermo re, if perfused cells were exposed to hyposmotic conditions, they swel led and underwent RVD provided that [Ca2+](i) buffering was low (with 2 mM EGTA). This effect was inhibited by presence of the cAMP antagoni st, [R]-p-adenosine 3',5'-cyclic monophosphorothioate.