Substance P is a functional neurotransmitter in the rat parotid gland.

Abstract

SUMMARY1. The technique of electrical field stimulation was employed to stimulate the intrinsic nerves ofisolated rat parotid gland fragments. Responses to field stimulation were recorded as changes in enzyme secretion (amylase release), radiolabelled ion fluxes (86Rb efflux) and electrophysiological effects (changes in acinar cell membrane potential and input resistance). All effects of field stimulation were abolished by the neurotoxin, tetrodotoxin (TTX).2. Selective use ofpharmacological antagonists revealed that both the sympathetic and parasympathetic nerves to this tissue were being excited by field stimulation. Importantly a significant component of the response to field stimulation persisted in the presence of combined autonomic receptor blockade by atropine, phentolamine and propranolol, i.e. due to release of a non-cholinergic, non-adrenergic neurotransmitter.3. The non-cholinergic, non-adrenergic neurotransmitter evoked amylase release, 86Rb efflux and electrophysiological effects seen as changes in acinar cell membrane potential and conductance, i.e. stimulus-permeability coupled.4. Two biologically active peptides, substance P (SP) and vasoactive intestinal polypeptide (VIP) were shown to evoke amylase release in the presence of combined autonomic blockade. VIP however did not evoke any increase in 86Rb efflux, i.e. not stimulus-permeability coupled. All the effects of the non-cholinergic, non-adrenergic transmitter were mimicked by substance P which evokes 86Rb efflux and electrophysiological effects in addition to amylase release.5. The non-cholinergic, non-adrenergic field stimulus effects on amylase release and 86Rb efflux were abolished or markedly attenuated in tissues which had been desensitized by prior exposure to exogenous substance P. In the presence of VIP, however, the non-cholinergic, non-adrenergic effects persisted and were apparently potentiated.6. Acute application of the neurotoxin capsaicin first stimulated a transient release of amylase and subsequently abolished the non-cholinergic, non-adrenergic field stimulus-evoked enzyme release.7. The putative substance P antagonist, D-Pro2, D-Trp7'9 substance P, reversibly blocked the response to both non-cholinergic, non-adrenergic nerve stimulation and exogenous substance P. It was demonstrated however that prolonged exposure to this 16-2 D. V. GALLACHER antagonist is associated with non-reversible and, importantly, non-specific neurotoxic effects.8. It is concluded that substance P or a closely related peptide is a functional neurotransmitter in the rat parotid gland.

Neuropeptide K potently stimulates salivary gland secretion and potentiates substance P-induced salivation.

“…SP has been shown previously to be a potent sialagogic peptide in the rat (16,17), and the response is mediated by interaction of SP with an SP-P (NK-1)-type receptor in parotid and submandibular gland membranes (14,(18)(19)(20)(21). Initially, we compared the time course of the salivation response in anesthetized rats injected intravenously with various doses of SP and with other peptides potentially derived from the f-PPT precursor.…”

“…Since [D-Pro2,D-Trp7'9]SP but not atropine antagonizes the salivation response induced by NPK, it would appear that the response is mediated by a tachykinin receptor. This antagonist appears to interact with more than one tachykinin receptor subtype, since it blocks tachykinin responses mediated by the SP-P (NK-1) type receptor (21,22) as well as that by the so-called SP-E (NK-3) type receptor (23 (17,26,27). If NPK interacts with this receptor system, the desensitization response may be different.…”

Potassium uptake in the mouse submandibular gland is dependent on chloride and sodium and abolished by piretanide.

“…The effluent from the tissue chamber was passed directly to a Corning (U.K.) model 480 flame photometer and the [K+ ] Field stimulation was achieved by means of silver electrodes implanted into the flow chamber (Gallacher, 1983;Fuller & Gallacher, 1984 Fig. 1 A is the total blockade of the field-stimulus effects upon introduction of the autonomic blockers atropine (10-5 M), phentolamine (10-5 M) and propranolol (5 X 10-6 M).…”

Proceedings of the Physiological Society, 11‐12 November 1983, Queen Elizabeth College, London Meeting: Communications

“…In this study the technique of electrical field stimulation (FS) was used (Gallacher & Petersen, 1980;Gallacher, 1983) to investigate for the first time the role of the intrinsic nerves in the activation of beta-adrenoceptor mechanisms in the isolated rat parotid gland. Parotid segments were superfused with physiological saline solutions containing atropine (10-5 M) and phentolamine (10-5 M).…”