Secretory regulation by cholecystokinin in the rat submandibular gland
1998 Volume 40 Issue 4 Pages 213-219
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1998 Volume 40 Issue 4 Pages 213-219
The functional role of cholecystokinin (CCK) as a neurotransmitter or neuromodulator in the parasympathetic salivary secretion in the rat submandibular gland was examined. A continuous infusion (20 μl/min) of CCK octapeptide (CCK-8) at 10-12-10-8M through the glandular artery caused salivary secretion in a dose-dependent manner, and the maximal secretory response was obtained at 10-10M. Atropine (cholinergic muscarinic antagonist, 1mg/kg, iv) reduced the salivary secretion induced by the infusion of 10-12-10-10M of CCK-8, but not 10-9 or 10-8M. The chorda (parasympathetic secretory nerve) was stimulated at various frequencies (0.5-60Hz) before and after the administration of the CCK-antagonist, CR1409 (10-4M). The salivary flow increased in a frequency-dependent manner, and the maximal responses were obtained at 20-40Hz with or without the CR-1409. The antagonist reduced the salivary flow at 20-60Hz, but had no effect at lower frequencies of 0.5-10Hz. The submandibular salivary flow, evoked by stimulation of the superior cervical ganglion (sympathetic secretory nerve), was not affected by the CCK-antagonist. Thus, CCK-8 may affect the submandibular acinar cells through at least two distinct pathways; in the first, CCK-8 stimulates the secretory response directly through the specific CCK receptor at the acinar cells (as a neurotransmitter). This pathway was blocked by a CCK-antagonist but not by atropine. Secondly, the effect of CCK-8 is modulated by interactions with the cholinergic receptor (as a neuromodulator). Immunohistochemical observations of CCK revealed that most nerve cell bodies within the submandibular ganglion were strongly CCK-positive and that some CCK-positive nerve fibers were distributed around acini in the gland. Both the immunohistochemical and physiological findings strongly suggested that the endogenous CCK directly and indirectly contributed to secretory regulation through parasympathetic innervation in the rat submandibular gland, with regard to the control of salivary fluid secretion.
