Basolateral adrenoceptor activation mediates noradrenaline-induced Cl- secretion in M-1 mouse cortical collecting duct cells.

Abstract

Noradrenaline (NA) released from efferent renal sympathetic nerves may directly affect renal tubular transport. Here we examined the effect of NA on transepithelial ion transport of cultured M-1 mouse cortical collecting duct cells using equivalent short-circuit current ( I(SC)) measurements. Steady-state I(SC) averaged 87.5+/-2.9 microA cm(-2) (n=185) and was reduced by 97.1+/-0.1% (n=80) by apical amiloride (100 microM) confirming that the predominant electrogenic transport across M-1 monolayers is sodium absorption via the epithelial sodium channel (ENaC). Basolateral addition of NA (10 microM) induced a biphasic change in I(SC) characterized by an initial transient peak increase of 18.1+/-0.9 microA cm(-2) with a subsequent decline to a plateau 1.4+/-0.3 microA cm(-2) (n=20) above baseline. Apical application of NA had no effect. The response to basolateral NA was concentration dependent and was preserved in the presence of apical amiloride. In contrast, the response was largely reduced in the presence of apical diphenylamine-2-carboxylic acid (1 mM) and in the absence of extracellular Cl(-). The peak response to NA was reduced in the presence of the alpha-adrenoceptor antagonist phentolamine (100 microM), whereas the beta-antagonist propranolol (100 microM) reduced the secondary plateau phase while failing to influence the peak response. The alpha(1)-adrenoceptor-selective antagonists prazosin (10 nM) and corynanthine (1 microM) reduced the NA-induced peak response by about 75% and 70%, respectively, while the alpha(2)-adrenoceptor antagonist yohimbine (100 nM) was ineffective. We conclude that in M-1 cells NA stimulates Cl(-) secretion probably involving both alpha(1)- and beta-adrenoceptors located basolaterally.