SALIVATION TRIGGERED BY PILOCARPINE INVOLVES AQUAPORIN-5 IN NORMAL RATS BUT NOT IN IRRADIATED RATS

Authors


Tetsuya Asari, Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd, 4365-1, Kashiwabara, Hotaka, Azuminno-city, Nagano Prefecture 399-8304, Japan. Email: tetsuya_asari@pharm.kissei.co.jp

SUMMARY

  • 1Using rats, we examined the muscarinic receptor subtype mediating pilocarpine-induced parotid salivary secretion and the contributions of ion transporter systems (effluxes of K+ and Cl-) and aquaporin-5 (AQP5) translocation to this response in parotid glands in irradiated-induced xerostomia.
  • 2Salivary secretion was significantly lower in irradiated compared with sham-irradiated (normal) rats. In xerostomia rats, 0.4 and 0.8 mg/kg pilocarpine significantly increased parotid salivary secretion, although the salivary volume was still significantly less than in normal rats after the same dose of pilocarpine.
  • 3Pirenzepine (1 × 10−6 to 1 × 10−1 mol/L), AF-DX 116 (3 × 10−6 to 3 × 10−2 mol/L) and N-2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP; 1 × 10−8 to 1 × 10−2 mol/L) dose-dependently displaced radioligand binding to M1, M2 and M3 receptors, respectively, in parotid membranes from both normal and irradiated rats. In each group of rats, 4-DAMP had the highest binding affinity. Pretreatment with 4-DAMP or pirenzepine dose-dependently inhibited pilocarpine-induced parotid secretion in both normal and irradiated rats, with 4-DAMP being markedly more potent than pirenzepine.
  • 4Normal and irradiated-rat parotid cells did not differ significantly in terms of pilocarpine-induced changes in [Ca2+]i, [K+]i and [Cl-]i. Pilocarpine markedly increased the amount of AQP5 in the apical plasma membrane of parotid cells isolated from normal but not irradiated rats.
  • 5Thus, pilocarpine induces parotid salivary secretion mainly via the M3 receptor subtype in both irradiated and normal rats. The reduction in this pilocarpine-induced secretion seen in irradiated rats is due not to disturbances of intracellular Ca2+ mobilization or ion transporter systems, but rather to a disturbance of AQP5 translocation, which may be involved in the pathogenesis of X-ray irradiation-induced xerostomia.

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