Effect of a-Receptor Stimulation on Cl Transport by Rat Submandibular Acini

Abstract

Dispersed salivary acini isolated from the rat submandibular gland by enzymatic digestion were used to study the effects of a-receptor stimulation on transmembrane transport of ³⁶Cl. In the absence of secretagogue, the tracer accumulated in the cells in a time-dependent manner until a steady-state content of 6.8 ± 0.1 nmol/mg protein was attained after 3-5 min of incubation. Epinephrine (1 μmol/L) alone did not modify ³⁶Cl accumulation but in the presence of the β-receptor blocker propranolol (1 μmol/L) caused a significant (21%) reduction in the isotope content of the cells to 5.2 ± 0.1 nmol/mg protein. In acini pre-loaded with ³⁶Cl for 12 min, 1 μmol/L epinephrine caused a rapid but transient net efflux of tracer, but the isotope content subsequently increased to pre-stimulation levels. In the presence of propranolol, however, the efflux of ³⁶Cl induced by epinephrine was larger and more sustained and was partially inhibited by the K-channel blocker quinidine (1 mmol/L) and significantly by the absence of Ca²⁺ in the incubation medium. The a-agonist phenylephrine (10 μmol/L) also significantly reduced the steady-state ³⁶Cl content of tracer-pre-loaded cells. By contrast, exposure of the acini to epinephrine in the presence of the a-receptor blocker phentolamine, or the β-agonist isoproterenol, increased the tracer content of the cells, whether the drugs were added at time zero or to tracer-pre-loaded cells. The results indicate that stimulation of a-receptors in salivary acinar cells causes a Ca²⁺-dependent efflux of Cl which seems to be functionally linked to K release. These effects are similar to those observed following stimulation of cholinergic receptors. The lack of effect of β-receptor stimulation on Cl efflux suggests that this response is not regulated by a cAMP-mediated pathway in salivary cells. The extent of stimulation-induced Cl efflux is likely to be relevant in terms of the amount of saliva secreted upon stimulation.