Abstract
In the in vivo experiments on anaesthetized sheep, it was presently examined whether muscarinic receptor antagonists with diverse selectivity affect the release of VIP in response to electrical stimulation of the parasympathetic chorda tympanic nerve differently, and if the changes in the release could be associated to altered secretory and vasodilator responses. The location of the muscarinic receptor subtypes was examined also. In the experiments, blood was collected out of the submandibular venous drainage before and during electrical stimulation of chorda tympani nerve in the absence and presence either of pirenzepine or methoctramine. While metchoctramine increased the output of protein, pirenzepine inhibited flow of saliva and increased protein output, vasodilatation, and VIP output. In morphological examinations, the inhibitory muscarinic M4 receptor occurred interacinarily in the gland. It is concluded that prejunctional muscarinic receptors, most likely of the M4 subtype, exert inhibitory modulation of the parasympathetic release of VIP in the ovine submandibular gland.
Highlights
The fluid secretory response of the ovine submandibular gland to acetylcholine is exerted via both muscarinic M1 and M3 receptors, while M5 receptors seem to participate in the cholinergic vasodilator response [1]
vasoactive intestinal peptide (VIP) is remarkably potent in eliciting protein secretion from salivary glands in a number of species [7,8,9,10,11], and VIP seems to play a role in human submandibular glands both regarding secretion and vasodilatation [12,13,14]
Electrical stimulation of the chorda tympani at 8 Hz evoked a mean flow of saliva over the 10minutes stimulation at of 78±3 and 59±4 μl min−1 g gland−1 before administration of pirenzepine and methoctramine, respectively
Summary
The fluid secretory response of the ovine submandibular gland to acetylcholine is exerted via both muscarinic M1 and M3 receptors, while M5 receptors seem to participate in the cholinergic vasodilator response [1]. In the submandibular gland of the sheep, VIP is present in nerve terminals adjacent to both small blood vessels and acini [3] In this gland as well as in the ovine parotid gland, VIP mediates secretion of protein-rich submandibular saliva, in addition, the vasodilator effects [4,5,6]. Unselective muscarinic receptor blockade of prejunctional receptors has been shown in a number of species to increase VIPergic responses together with the release of VIP upon electrical stimulation of the parasympathetic glandular innervation [6, 18, 19]. VIP is preferentially released during intense parasympathetic stimulation [20] It was presently wondered whether or not blockade with muscarinic receptor antagonists with different selectivity profile affects the release of VIP in response to electrical
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