Action of physalaemin on the ionic transport across the frog skin.
The effects of the non-mammalian tachykinin physalaemin were studied on the short circuit current (SCC) and on both influx (Ji) and outflux (Jo) of 36Cl- and 22Na+ across the isolated skin of Rana esculenta. Physalaemin, added to the internal bathing fluid, increased SCC in a dose-dependent manner with a maximal effect at 1 microM. This increase was due to a stimulation of both Na+ absorption and Cl- secretion. Bumetanide (20 microM in the internal fluid), an inhibitor of the Na+/K+/2Cl- cotransporter, reduced the action of physalaemin on SCC by 46%. Furthermore diphenylamine-2-carboxylic acid (DPC, 0.1 mM in the external fluid), an inhibitor of Cl- channels, decreased the effect of the peptide on SCC by 48%. It is concluded that physalaemin activates the Na+/K+/2Cl- cotransporter at the basolateral membrane, accumulating Cl- in the cells and favouring its exit through Cl- channels at the outermost membrane of the epithelium. An inhibitor of cyclooxygenases, i.e. naproxen, strongly inhibited the physalaemin effect on SCC, whereas 5,8,11-eicosatriynoic acid (ETI), an inhibitor of lipooxygenases was without effect. Therefore, it is proposed that prostaglandins (probably PGE2) are the cellular mediators of this action. An antagonist of NK1 receptors for tachykinins, CP 99,994, inhibited the physalaemin action on SCC, whereas challenge with SR 48,968, an antagonist of NK2 receptors, had no effect on physalaemin action. It is concluded that physalaemin effect on SCC in frog skin is mediated by its interaction with NK1 receptors.
Institute of General Physiology, University of Bari, Italy.
S
S
Lobasso
C
C
Lippe
V
V
Bellantuono
C
C
Ardizzone
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects*; D010803:Physalaemin / Q000494:pharmacology*; D011893:Rana esculenta; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000819:agonists*
D010803:Physalaemin; D016718:Arachidonic Acid; D013373:Substance P