Depletion of acinar secretory granules in the ferret parotid gland: effects of substance P and vasoactive intestinal peptide

Abstract

SUMMARYThe acinar cells of the ferret parotid gland are supplied with parasympathetic nerve fibres containing vasoactive intestinal peptide (VIP) and substance P. In this study intracarotid infusions of the two peptides (0-5-1-0 #g kg-min-1 of each for 40 min) in the pentobarbitoneanaesthetized ferret, treated with atropine and adrenoceptor antagonists, induced a loss of acinar secretory granules from this gland, by 32% in response to VIP and by 46% in response to substance P. Stimulation of the parasympathetic auriculo-temporal nerve (40 Hz, in the presence of adrenoceptor antagonists) caused a larger loss of acinar granules from the gland than stimulation of the sympathetic superior cervical ganglion (intermittently, 50 Hz for 1 s every 10th second, in the presence of atropine) over 40 min (52 % versus 10 %). A 27 % granular loss in response to parasympathetic stimulation followed upon atropinization. The parasympathetic response was not further diminished by the tachykinin antagonist Spantide ((D-Arg',D-Pro2, D-Trp7 9,Leu)-substance P). Thus, despite the large exocytotic response to the infusion of substance P, the parasympathetic non-adrenergic, non-cholinergic secretion of storage granules seemed, under the present experimental conditions, to occur independently of the action of substance P.

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

“…In the first series of experiments, a 20% reduction in flow rate may be attributed to the action of the antagonist, whereas in the second series of experiments, the flow rate was reduced by as much as 50–70% and the secretory response to a bolus dose of substance P was reduced by 70–85%. The inhibitory action of the substance P‐antagonist currently used on salivary secretion has previously been demonstrated in the rat and the ferret (Ekström and Olgart, 1985; Bobyock et al , 1986; Ekström, 1998; Ekström and Ekström, 1998). At the low dose of the antagonist (0.25 mg kg −1 ), the substance P response at 0.5 μg kg −1 is reduced by 44% (Ekström and Olgart, 1985).…”

“…At the high dose of the antagonist, an effect on the blood pressure cannot be excluded, as it was not measured. Although the currently used substance P‐antagonist, at the high‐dose level, and a structurally related substance P‐antagonist, did not per se affect the blood pressure or the glandular blood flow (Tobin et al , 1991; Ekström and Ekström, 1998), the substance P‐antagonist spantide has been reported to cause a marked fall in blood pressure (Delbro, 1987). The functional and seemingly compelling evidence in favour of substance P receptor‐mediated secretion currently found is at variance with the only binding assay on record with respect to substance P and olanzapine.…”

“…The secretory response to the standard doses of methacholine and substance P currently used is prompt, within a few seconds upon their intravenous administration, and the duration of the response is short, 1–2 min. The dose range chosen for the neuropeptide antagonists was taken from the literature (Ekström and Olgart, 1985; Bobyock et al , 1986; Ekström, 1998; Ekström and Ekström, 1998; Garcia‐Nicas et al , 2001; Juhl et al , 2006; Martinez et al , 2006).…”

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

“…It is therefore possible that amisulpride, without causing any overt fluid secretion of its own, may in humans potentiate the action of various transmitters evoking salivary secretion as is the case in the rat (Godoy et al , ). A positive interaction between an agonist just evoking exocytotic activity and no flow of saliva, and agonists evoking the secretion of saliva is, for instance, well known from experiments on cats with respect to vasoactive intestinal peptide and muscarinic agonists (Lundberg et al , ; Ekström et al , ) and on ferrets with respect to vasoactive intestinal peptide and muscarinic agonists or substance P (Ekström et al , ; Ekström and Ekström, ). Consequently, weight is gained for the idea that the molecule of amisulpride may be a useful starting point for the development of drugs, perhaps locally applied on the oral epithelium (Khosravani et al , ), to enhance the autonomic nervous tone on the underlying minor salivary glands aiming at treating salivary gland hypofunction.…”

Secretion from submucosal salivary glands of the ferret in response to a cholinesterase inhibitor applied onto the oral mucosa

“…This conclusion is supported by recordings of the blood pressure and the secretion from the parotid and submandibular glands. No saliva appeared from the submandibular gland, and the rate of parotid secretion occurring at the highest concentration of physostigmine was less than 3% of that in response to parasympathetic stimulation applied at frequencies of 10–40 Hz (15, 16).…”