N. Emmelin

Nerve Interactions in Salivary Glands

In the salivary reflex, not only secretory cells are activated, but also myo-epithelial cells are contracted to support these cells and promote the flow of saliva, and blood vessels dilate to meet the increased demands of the tissues. The various effector cells often receive nerves from both parts of the autonomic system, and interactions may occur when the nerves act on the same type of effector, or on different types of effectors. While in an experiment electrical stimulation of the sympathetic trunk may decrease a parasympathetic salivary flow by causing marked vasoconstriction, this does not occur in the salivary reflex, since the vasoconstrictors do not take part. On the contrary, the normal sympathetic vasoconstrictor tone of the resting gland is easily overcome by activity in parasympathetic vasodilator nerves when secretion starts. Pronounced synergism can be demonstrated between sympathetic and parasympathetic secretory nerves. In dogs, for instance, in which sympathetic secretion is β-adrenoceptor-mediated, this is marked in the case of fluid secretion. In rats and rabbits, in which β-receptors elicit secretion of amylase, the potentiating interaction among the nerves is striking when amylase secretion is considered. Even the random release of acetylcholine from the post-ganglionic parasympathetic axons, by itself insufficient to evoke secretion, can increase the sympathetic effects. Motor nerves interact with secretory nerves by causing myo-epithelial contraction, mechanically promoting secretion. Interactions between the nerves in their long-term regulatory function on the sensitivity of the acinar secretory and myo-epithelial cells can also be demonstrated.

Action of transmitters on the responsiveness of effector cells

Die Regulation der Empfindlichkeit der Effektorzellen ist in der vorliegenden Übersicht an Speicheldrüsen, hauptsächlich an der Submaxillarisdrüse als Modell untersucht worden. Es entwickelt sich eine gesteigerte Empfindlichkeit, wenn man die Verbindung mit dem zentralen Nervensystem durch chirurgische Dezentralisierung oder durch Behandlung mit ganglienblockierenden Substanzen unterbricht. Eine gewisse Sensibilisierung kann auch erhalten werden, indem man die afferenten Nervenfasern im sekretorischen Reflexbogen durchschneidet. Die Versuche deuten darauf hin, dass der sekretorische Impuls eine Rolle bei der Regulation des Empfindlichkeitsniveaus spielt. Dass dieser Effekt ebenso wie der sekretorische durch Acetylcholin vermittelt wird, geht daraus hervor, dass Sensibilisierung eintritt, wenn das Versuchstier mit Botulinustoxin behandelt wird, da dieses die Freisetzung von Acetylcholin verhindert, oder durch Atropinsubstanzen, die die Wirkung des Acetylcholins auf die Drüsenzellen verhindern. Andererseits kann eine durch parasympathische Dezentralisierung hervorgerufene Sensibilisierung durch tägliche Injektionen von Pilokarpin, Mecholyl oder Physostigmin aufgehoben werden; auch das normale Empfindlichkeitsniveau kann durch eine solche Behandlung gesenkt werden. Behandlung mit Botulinustoxin oder mit Atropinsubstanzen oder postganglionäre parasympathische Denervierung ergeben eine Sensibilisierung, die ausgesprochener ist als diejenige, welche auf parasympathische Dezentralisierung folgt. Diese und andere Beobachtungen deuten darauf hin, dass Acetylcholin ständig von den postganglionären Nervenendigungen abgegeben wird und dass dieses Acetylcholin, wie auch das von den Nervenimpulsen freigesetzte, die Empfindlichkeit der Effektorzellen kontrolliert. Entsprechend scheint Sympathin von den postganglionären sympathischen Nervenendigungen abgegeben zu werden und zur Regulation der Empfindlichkeit beizutragen; postganglionäre sympathische Denervierung ruft eine gewisse Sensibilisierung hervor, und eine Behandlung mit Bretylium oder Guanethidin hat den gleichen Effekt.

SECRETORY NERVES OF THE SALIVARY GLANDS

ABSTRACT Secretion can be evoked in salivary glands by electrical stimulation of both parasympathetic and sympathetic nerves. The present paper deals mainly with another important effect of these nerves on the gland cells, to which so far much less attention has been paid. This effect, just as the secretory one, is caused by the chemical transmitters. In addition to their immediate secretory action the transmitters exert a long-term effect on the gland cells, regulating the responsiveness of the cells to secretory stimuli. When the transmitters are prevented from acting on the gland cells for some time, changes occur in the cells which develop gradually and manifest themselves in an increasing responsiveness to secretory stimuli. To some extent this regulating effect is exerted by transmitter released by the secretory impulse from the central nervous system. This is shown for instance by the fact that the gland acquires a supersensitivity when the flow of secretory impulses is reduced by cutting afferent fibres of the secretory reflex arc. However, prolonged administration of drugs which prevent the release of transmitters from the nerve endings, or prevent the transmitters from attaching themselves to the gland cells, causes a supersensitivity much more pronounced than that produced by disconnecting the gland from the central nervous system by cutting the preganglionic autonomic fibres. These observations, together with others quoted in the present paper, demonstrate that the transmitter agents are released from the endings of the postganglionic fibres even in the absence of secretory impulses of central origin. They further indicate that transmitters thus continuously leaking take part in the regulation of the sensitivity of the gland cells, although their concentration normally remains subthreshold as far as secretion is concerned. The threshold for secretion can, however, be surpassed under special experimental conditions, for instance during a certain phase of degeneration of the postganglionic fibres. Parasympathetic fibres play the main role as mediators of secretory impulses, and correspondingly, acetylcholine is of great importance for the control of the glandular sensitivity. The experiments described suggest, however, that sympathine leaking from sympathetic endings also plays a role in this control. It has here so far been assumed that the salivary glands studied are supplied with sympathetic secretory fibres and, indirectly, the experiments just mentioned suggest this to be the case. Since, however, the existence of such fibres has been questioned by some investigators, the present paper is introduced by a brief discussion which gives arguments in favor of the view that specific sympathetic secretory fibres for salivary glands do exist and that a single salivary cell may receive secretory fibres from both divisions of the autonomic nervous system.

Amylase secretion from rat parotid glands as dependent on co-operation between sympathetic and parasympathetic nerves

A slow, long-lasting ‘degeneration secretion’ from the parotid gland was brought about in anaesthetized rats by section of the auriculo-temporal nerve 16–19 h in advance. This parasympathetic background activity greatly increased the secretion of amylase elicited by sympathetic nerve stimulation.

CONTROL OF SALIVARY GLANDS

Publisher Summary The function of the salivary gland system is characterized by the continuous resting secretion upon which intermittently an enormously increased activity is superimposed. The saliva manufactured by a single gland is highly variable. The gland consists of a number of different types of effector cells, concerned with the production and discharge of the saliva. The various cells of the acini are divided into serous and mucous cells. This chapter discusses the way the activity of these various effectors is regulated. In some salivary glands, the secretory machinery is permanently active, continuously producing and discharging saliva, even in the absence of extraneous stimuli. The salivary glands provide one of the best examples of a control mechanism exerted by a local hormone. The kinins of interest for the regulation of the blood flow, kallidin and bradykinin, have no secretory effect in the glands in reasonable dosage. The nerves play the main part in the control of salivary glands. After denervation or decentralization, many of the glands show considerable atrophy. As a long-term function, the nerves regulate the sensitivity of the gland cells to secretory stimuli, and it applies to the parasympathetic innervations.

Degeneration secretion of saliva in the rat following sympathectomy

1. After previous extirpation of the superior cervical ganglion saliva was found to flow from the cannulated submaxillary duct of rats under chloralose anaesthesia. The secretion started 13–14·5 hr after sympathectomy, increased gradually in rate and then slowed down and ceased, lasting for about 12 hr.

Action of Histamine upon Salivary Glands

The early papers on the pharmacology of histamine describe salivary secretion as a characteristic effect of this drug (Dale and Laidlaw, 1910; Barger and Dale, 1910; Ackermann and Kutscher, 1910; Frohlich and Pick, 1913). Intravenous injection of 2–10 mg histamine was found to cause a profuse secretion in unanaesthetized cats, and in anaesthetized cats and dogs histamine was observed to evoke a flow of saliva from the cannulated submaxillary duct.

Effects of guanethidine on salivary glands

Guanethidin hebt den sekretorischen Effekt der Sympathicusstimulierung von Speicheldrüsen genau so wirksam auf wie Bretylium. Ebenso wie Bretytylium kann Guanethidin eine Speichelsekretion hervorrufen, aber nur, wenn es in grosser Menge gegeben wird. Während Bretylium dabei einen Muskarineffekt hat, scheint Guanethidin durch Freisetzen von Catecholaminen an den sympatischen Nervenenden zu wirken.

Action of acetylcholine on the responsiveness of effector cells

Bei der Katze wird die Empfindlichkeit der Submaxillarisdrüse gegenüber chemischen Reizen verringert, wenn während zwei Tagen subkutane Eserin-injektionen verabreicht werden. Damit ist bewiesen, dass das Empfindlichkeitsniveau der Drüse von der Acetylcholinkonzentration abhängig ist.

Salivary secretion in dogs during degeneration of postganglionic parasympathetic nerve fibres

Eine sogenannte Degenerationssekretion erscheint beim Hund in den Tagen nach der postganglionär-parasympathischen Denervierung der Submaxillaris-und Sublingualisdrüsen.