Cytomorphological study on human submandibular gland following treatment with secretagogue drugs

Abstract

Using specimens of human submandibular glands, we have investigated in vitro the morphological modifications induced by clozapine, a dibenzodiazepine derivative that is used in psychotic patients and that provokes hypersalivation, a side-effect of therapy. The effects of the drug, used alone or in combination with carbachol, have been compared with those observed after treatment with drugs acting on specific receptors. To quantify the response to stimulation, we have calculated (with statistical methods) the number of microvilli and microbuds (corresponding to pits seen in images obtained by transmission electron microscopy) per square micrometre of the cytoplasmic surface of the intercellular canaliculi luminal membrane in images obtained by high-resolution scanning electron microscopy. Clozapine, when directly acting on human submandibular specimens, induces a small secretory response in serous cells; this is partially decreased by muscarinic and adrenergic antagonists and by combined incubation with carbachol, thus confirming its behaviour as a partial agonist to muscarinic receptors. We also suggests that the drug acts on the nerve terminals contained within the glandular specimens.

Clozapine: Agonistic and Antagonistic Salivary Secretory Actions

“…Likewise, ultrastructural changes evoked by carbachol in human submandibular tissue, indicating secretory activity, were partially reduced by clozapine (Testa Riva et al, 2006).…”

“…However, human submandibular gland tissue exposed to clozapine in vitro responded with ultrastructural changes reflecting secretory activity (Riva et al, 2003;Testa Riva et al, 2006).…”

The antipsychotic amisulpride: ultrastructural evidence of its secretory activity in salivary glands

“…Without causing any overt flow of saliva per se , amisulpride evoked cellular activities of the serous/seromucous cells of the parotid and submandibular glands both in vivo and in vitro that are usually associated with secretory activity. Samples not exposed to the drug only occasionally displayed granules anchored to the canaliculi membrane causing the phenomenon of protrusions, a phenomenon also occurring infrequently in in vitro control samples of human salivary glands (Testa Riva et al , ; Loy et al , ). In both types of gland, and regardless of whether in vivo or in vitro , the magnitude of the increase in the number of protrusions, expressed in terms of density, was about the same (submandibular glands 0.30–0.41 per μ m 2 and parotid glands 0.27–0.31 per μ m 2 ) in response to amisulpride with or without the autonomic receptor antagonists.…”

Salivary secretion effects of the antipsychotic drug olanzapine in an animal model

“…Experiments, using the rat as an animal model, show that clozapine, and its metabolite N ‐desmethylclozapine, exerts dual and opposite actions on the salivation (Ekström et al , 2010a,b; Godoy et al , 2011): a direct excitatory action on muscarinic acetylcholine receptors of the M1 type evokes a low‐grade continuous flow of saliva from the parotid and submandibular glands, and a direct, and marked, inhibitory action on the parasympathetically and sympathetically nerve‐evoked secretion by muscarinic acetylcholine receptors of the M3 type and by α 1 ‐adrenergic receptors. Moreover, the in vitro administration of clozapine induces ultrastructural changes in human submandibular gland tissue that is attributed to secretory activity (Testa Riva et al , 2006). It is therefore suggested that, during the night and during the day, at rest, the stimulatory action of clozapine dominates, while during a meal – increasing the secretory demands on the glands – the inhibitory action of the drug becomes dominant.…”