Etiology of xerostomia and dental caries among methamphetamine abusers.

This study reviews the peripheral effects of methamphetamine on the salivary acini, the pathogenesis of methamphetamine-induced xerostomia, and its anecdotal relationship to dental caries. Methamphetamine is a sympathomimetic central stimulant which is abused for its euphoric effects. Its pharmacological action is exerted indirectly by sustaining high levels of catecholamines in the synaptic cleft and directly by binding to the postsynaptic adrenergic receptors. Methamphetamine abusers report subjective perception of xerostomia, which cannot be explained by the direct peripheral action of methamphetamine on the secretory acini. The drug may cause a decrease in salivary flow rate by centrally inhibiting salivatory nuclei via stimulation of alpha-2 receptors in the brain. Drug mediated dehydration state may influence the perception of dry mouth in abusers. The decreased salivary flow rate, either due to a central inhibitory action of methamphetamine or generalised dehydration, likely contributes to the increased occurrence of dental caries. Five cases of methamphetamine abuse are presented, three of whom experienced rampant dental caries. A direct association between methamphetamine abuse and the occurrence of rampant caries was not clear.

Submandibular gland acinar cells express multiple alpha1-adrenoceptor subtypes.

We evaluated an acinar cell line (SMG-C10) cloned from rat submandibular glands as a possible model for alpha(1)-adrenoceptor regulation of submandibular function. alpha(1)-Adrenoceptors are subdivided into three subtypes called alpha(1A), alpha(1B), and alpha(1D), which can be distinguished from one another by their differential affinity values for subtype-selective alpha(1)-adrenoceptor antagonists. Thus, alpha(1)-adrenoceptor subtypes in SMG-C10 cells were characterized with reverse transcription-polymerase chain reaction (RT-PCR) and [(3)H]prazosin binding in side-by-side experiments with native submandibular glands. RT-PCR identified mRNAs for alpha(1A)-, alpha(1B)-, and alpha(1D)-adrenoceptors in SMG-C10 cells and submandibular glands. The inhibition of [(3)H]prazosin binding by 5-methylurapidil (alpha(1A)-selective) was biphasic and fit best to a two-site binding model with 40 +/- 8% high (K(iH))- and 60 +/- 10% low (K(iL))-affinity binding sites in SMG-C10 cells, and 76% high- and 24% low-affinity binding sites in submandibular glands. Respective K(iH) and K(iL) values for 5-methylurapidil were 1.9 +/- 0.4 and 100 +/- 30 nM in SMG-C10 cells and 3.2 +/- 0.8 and 170 +/- 20 nM in submandibular glands. BMY-7378 [8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride (alpha(1D)-selective)] bound with low affinity in SMG-C10 cells and submandibular glands with K(i) values of 81 +/- 20 and 110 +/- 20 nM, respectively. Chloroethylclondine, an irreversible alkylating agent selective for alpha(1B) adrenoceptors, reduced the density of [(3)H]prazosin binding sites by 42 and 26% in SMG-C10 and submandibular membranes, respectively. Thus, SMG-C10 cells and submandibular glands are similar in expressing receptor protein for alpha(1A)- and alpha(1B)-adrenoceptor subtypes, establishing SMG-C10 cells as a potential model for alpha(1)-adrenoceptor-mediated secretion.