F. Morel, S. Jard
Dec 1, 1971
Citations
0
Influential Citations
7
Citations
Journal
Annals of the New York Academy of Sciences
Abstract
The epithelial cells of the amphibian skin and bladder, as well as those of the kidney's distal tubule, represent systems whose osmotic permeability to water and Na transporting capacity are controlled by neurohypophysial hormone through the production of cyclic AMP as second messenger.?, 3 , 8 . 13, *O , 21 Experimental evidence favoring this general mode of hormonal action has been reviewed previous1y.l'. 22 When the regulatory role of cyclic AMP in cell activity is discussed, two main aspects may be considered: ( 1 ) the way in which hormones enhance the production of cyclic AMP within the cells (mechanism of adenyl cyclase regulation); and (2) the way in which intracellular cyclic AMP controls specific cell functions. As far as the permeability and transport properties of epithelial cells are concerned, little is known at the molecular level, so that any discussion of the mechanisms by which cyclic AMP could directly or indirectly control active sodium transport would be mainly speculative. That is why we shall restrict our discussion to some recent pharmacological observations concerning the first of the above points. The amphibian skin is a very convenient system for studying the mechanism of hormone action for both technical and biological reasons: (1) hormonal responses can be elicited reversibly and repeatedly in vitro on the isolated structure; (2 ) both the osmotic permeability to water and the active transport of sodium (short circuit current 2 5 ) can be quantitatively and continuously recorded as a function of time; n. l!' and (3 ) the physiological activity of the frog skin is under a plurihormonal control mediated by cyclic AMP, since not only are the neurohypophysial peptides active but norepinephrine as well." Therefore the question arises, and will be discussed, of deciding whether several adenyl cyclases are present or only a single one with multiple hormonal control. Both neurohypophysial peptides and the norepinephrine induce two different effects on the structure: increased osmotic permeability to water l1, and stimulation of the active sodium transport.". ll. 26 As will be shown, there are experimental conditions under which it is possible to observe some dissociation of the two effects; G , 7 . 2 q this raises the problem of the functional compartmentalization of the cyclic AMP pools within the target cells, since it is generally assumed that both effects are elicited in the same cells. Nevertheless, it must be stressed that the epithelial layers represent a very small fraction of the whole skin. and that other types of cells, like chromatophores. are known to respond to specific hormonal stimulation by increased cyclic AMP production 1, when the whole structure is used. Such histological heterogeneity precludes any precise correlation between the physiological observations and biochemical measurements (like cyclic AMP concentrations). Fortunately, it is now possible to prepare large sheets of isolated skin epithelium by appropriate pretreatment of the ventral frog skin with collagenase and hydrostatic pressure.2y All the data collected by our group and reported in this paper were recently obtained by using such a preparation.*:' Morphological