EFFECTS OF 2ND MESSENGERS ON THE PERMEABILITY AND MORPHOLOGY OF EEL RETE CAPILLARIES

The effects of second-messenger concentration changes on capillary dif fusion capacity (permeability-surface area product [PS]) to cellular a nd paracellular tracers and on capillary ultrastructure were studied d uring countercurrent perfusion of the rete of the eel swim bladder. Cy clic nucleotide effects were investigated with isoproterenol, forskoli n, and dibutyryl cAMP. Isoproterenol (5x10(-6) mol/L) did not modify w ater and solute permeability or capillary structure. Forskolin (10(-4) mol/L) immediately raised the concentrations of cAMP in the rete and produced interstitial edema but did not change permeability. The addit ion of dibutyryl cAMP (10(-6) mol/L) to the perfusate had rapid effect s: it reduced the PS of [H-3]water and oxygen and increased the PS of [I-125]albumin, [C-14]sucrose, and Na-22. No structural changes were o bserved. Phosphoinositide effects were studied with 1,2-dioctanoyl-sn- glycerol (DG) and phorbol 12-myristate 13-acetate (PMA). DG (10(-5) mo l/L) had no effect on the permeability of the rete to water and solute s, while inducing cell membrane vacuolization. PMA (10(-5) mol/L) prog ressively reduced the PS of [H-3]water. In contrast, PS values of [I-1 25]albumin, [C-14]sucrose, and Na-22 rose gradually. Membrane vacuoles bulging into the lumen and in the cytoplasm were a common feature. Th e Ca2+ effect was investigated with the Ca2+ ionophore A23187. At 5x10 (-6) mol/L, unsteady permeability changes and extensive cytolysis were observed. At 5x10(-7) mol/L, the PS of [I-125]albumin, [C-14]sucrose, and Na-22 rapidly increased. The PS values for water were not modifie d. No structural changes were identified. It is concluded that increme nts of second-messenger concentrations in the rete induce characterist ic selective effects on the paracellular and transcellular pathways of transport and create significant but nonselective alterations of capi llary structure.