Cyclic nucleotides and their role in gastrointestinal secretion.

Mucosal hypertonicity, produced by the addition of NaCl, KCl, mannitol, urea, sucrose or raffinose, reduced the electrical resistance of toad urinary bladder and induced bullous deformations (blisters) of the most apical junctions of the mucosal epithelium: the smaller solutes were most effective in eliciting both phenomena. Study of the effect of addition and subsequent removal of mannitol from the mucosal medium indicated that both the electrical and morphologic changes are reversible and follow the same time course. Mucosal hypertonicity induced comparable changes in the tissue in the presence or absence of inhibition of active sodium transport by replacement of sodium by choline, or by addition of ouabain or amiloride. Dilution of the tonicity of the serosal medium similarly reduced the tissue resistance and induced blisters within the epithelium, demonstrating that the osmotic gradient, rather than the mucosal hypertonicity itself is the cause of the osmotically-induced resistance change. The data indicate, therefore, that the osmotic gradient reduces the electrical resistance of the tissue primarily by deforming the apical junctions. The simplest interpretation of the data is that the apical tight junctions are considerably more permeable to water and small solutes than had previously been thought. Addition of solute to the mucosal medium leads to the diffusion of solute into the junctions: the subsequent transfer of water from the lateral intercellular spaces and/or the adjacent cellular cytoplasm, deforms these structures and reduces the resistance to the passage of ions across the tissue. The results suggest that the apical junctions constitute the rate-limiting permeability barrier of the putative parallel shunt pathway across toad bladder.

Pathways for movement of ions and water across toad urinary bladder. I. Anatomic site of transepithelial shunt pathways.

Adenyl cyclase activity was assayed in crude homogenates of the renal cortex, medulla, and papilla of the golden hamster. The specific activity (moles C-AMP/unit of time per mg protein of tissue) of the enzyme under basal conditions, was greatest in papilla, somewhat lower in medulla, and least in cortex. On an absolute scale, the sensitivity to vasopressin was greater in the medullary and papillary than in the cortical homogenates. In addition, at concentrations of 0.1-1.0 mm, CaCl(2) inhibited the enzyme in the order papilla > medulla > cortex. These results imply the existence of distinct differences in the composition of the adenyl cyclase-receptor complex in various parts of the kidney. We proposed that Ca(++) inhibits the core enzyme directly since at the minimally inhibitory concentration (0.1 mm), CaCl(2) reduced to an equivalent extent (a) basal activity, (b) the response to graded doses of vasopressin (0.5 to 50.0 mU/ml) and (c) the response to maximal stimulatory concentrations of NaF (10 mm). Prostaglandin E(1) (PGE(1) = 10(-7)m) had no effect on either basal adenyl-cyclase activity or the response to 10 mm NaF in medullary and papillary homogenates. 7-Oxa-13-prostynoic acid (10(-4)m) similarly had no effect under basal conditions or on stimulation with NaF in medullary homogenates. Both fatty acids, however, inhibited the enzymic response to vasopressin, particularly at low concentrations of the peptide. The straight-chain fatty acid, 11-eicosanoic acid (10(-7)m), was inactive on basal activity or on the response to vasopressin. The possibility that PGE(1) modifies the coupling mechanism between the core enzyme and the hormone-specific receptor is discussed.

/pdf/effects-of-ca-and-prostaglandin-e1-on-vasopressin-activation-4xccpjrl54.pdf

Effects of Ca++ and prostaglandin E1 on vasopressin activation of renal adenyl cyclase.

Experiments were carried out with the isolated, perfused cat spleen and bovine splenic nerve trunk to study the target for prostaglandin E2 induced inhibition of noradrenaline release from sympathetic nervss. Increasing the calcium concentration in the medium perfusing the spleeen was found to increase the outflow of noradrenaline to nerve stimulation and to antagonize the inhibitory action of prostaglandin E2 on this parameter. Prostaglandin E2 did not affect the noradrenaline releasing effect of tyramine. Atropine did not alter the inhibitory effect of prostaglandin E2 on noradrenaline release. Prostaglandin E2 did not change the amplitude of action potentials in bovine splenic nerves. There is thus no support for a blocking action on nerve conduction. It is concluded that prostaglandin E2 may prevent calcium from gaining access to those sites in sympathetic nerve terminals where it promotes secretion of noradrenaline.

Argy Wp

Papers

Ca++ and Mg++ effects on toad bladder response to cyclic AMP, theophylline, and ADH analogues.