A tentative explanation of the stimulatory effect of methylxanthines (pentoxifylline and isobutylmethylxanthine) on the secretory process in rat extraorbital lacrimal gland

In the present paper we report the effect of two methylxanthines (pentoxifylline and isobutylmethylxanthine) on the protein secretion in a model of exocrine gland (rat lacrimal gland). Both compounds are able to increase the protein release. This effect is dependent on the calcium concentration gradient between the extra- and intracellular media. The larger the difference, the greater the pentoxifylline or isobutylmethylxanthine effect. Moreover, pentoxifylline and isobutylmethylxanthine can potentiate the norepinephrine or isoproterenol effect by inhibiting phosphodiesterases (even in the absence of calcium). All these data suggest pentoxifylline and isobutylmethylxanthine can act on the cell functions in two ways: (a) by a calcium-dependent mechanism, either by increasing the influx of calcium into the cell or by mobilizing the pool of intracellular calcium; (b) by a mechanism independent of calcium and dependent on a system involving cyclic nucleotides. The first possibility seems to be very attractive for further investigations of the mechanism of action of pentoxifylline and especially when this drug is used to affect the cell motility or deformability controlled by calcium.