C. A. Schneyer

SALIVARY GLAND ATROPHY IN RAT INDUCED BY LIQUID DIET.

Summary A diet of liquid ration (either Metrecal or liquid homogenized chow) caused atrophy of all major salivary glands in rats. No nutritional inadequacy accounted for the effects. The glands, as well as the acinar cells of these tissues, were markedly reduced in size; ducts were not appreciably altered. The parotid gland, the most affected of the 3, exhibited a decrease in amylase in the gland as well as in the secretion, but no appreciable change in concentration of Na and K in the secretion was noted. The functional and structural changes observed occur despite an intact innervation and suggest that activity of the glands, dissociated from neurotrophic influences, plays a major role in maintenance of gland integrity.

Role of β-receptors in sympathetic regulation of electrolytes in rat submaxillary saliva

Summary Electrolyte composition ([K], [Na], [Cl], [HCO3]) and flow rate have been characterized in rat submaxillary saliva evoked by electrical stimulation of the sympathetic innervation. [K] and [HCO3] were found to be appreciably higher, and flow rate lower, in sympathetically than in parasympa-thetically evoked saliva. Administration of the β-adrenergic blocking agent, Inderal, prior to sympathetic stimulation resulted in significant reduction in salivary [K] of pilocarpine-evoked saliva but did not affect the electrolytes of saliva obtained by stimulation of the parasympathetic innervation. It is concluded that in rat submaxillary gland β-adrenergic receptors are involved in regulation of electrolyte composition by sympathetic nerves and by the adrenergic component of the action of pilocarpine.

Autonomic Pathways Involved in a Sympathetic-Like Action of Pilocarpine on Salivary Composition.

Summary When stimulation of the rat parotid gland was effected by pilocarpine administration immediately following removal of one superior cervical ganglion, the amylase levels in the secretion obtained from the denervated gland were approximately 1/10 the levels obtained from the normally innervated gland, and were very similar to levels obtained as the result of stimulation of the auriculo-temporal nerve, or following administration of the β-adrenergic blocking agent Inderal prior to pilocarpine stimulation. On the other hand, amylase levels of pilocarpine-evoked saliva were not modified either by severing of the preganglionic fibers to the superior cervical ganglion or by removal of both adrenal glands. It is concluded that the sympathetic-like character of pilocarpine-evoked saliva results from an indirect stimulation of adrenergic receptors in the gland that is mediated through the superior cervical ganglion and the sympathetic postganglionic fibers.

β-Adrenergic Effects by Autonomic Agents on Mitosis and Hypertrophy in Rat Parotid

Summary A series of sympathomimetic and parasympathomimetic agents were administered chronically to rats. At 3 and 10 days, the effects of these agents [the β-adrenergic drug, ISO; the primarily α-adrenergic drugs, epinephrine and phenylephrine, and the parasympathomimetic agents, pilocarpine (PC) and Urecholine (UR)] on parotid gland weight, and size and mitotic activity of acinar cells were examined. It was found that mitotic activity was observed only under those conditions where activity of β-adrenergic receptors could be implicated (ISO, PC, and UR), and the β-blocking agent, Inderal, was used to demonstrate this point. Increases in cell and gland size more generally accompanied β-adrenergic activity and were evident even in the absence of a distinct mitotic response; α-mediated effects, however, produced no mitotic effects but instead decreased cell and gland size. Secretory activity was not necessarily involved in any of the β-adrenergically mediated increases in gland size, acinar cell size or number.

Increased Chromosome Number of Rat Parotid Cells After Isoproterenol.

Summary Administration of pharmacologic doses of the sympathetic amine, isoproterenol, to adult female rats resulted in a progressive enlargement of the gland with duration of treatment. Although this enlargement is the result of hypertrophy of acinar cells as well as proliferation of these elements, marked mitotic activity was generally confined to the early days of treatment (1-5 days) whereas hypertrophy was initiated almost immediately and persisted throughout the period of isoproterenol-administration. During the early phase of marked cellular proliferation, chromosome counts from squash preparations of tissue indicated that greater-than-diploid (>2n) as well as diploid (2n) cells were present. Furthermore, the proportion of 2n to >2n changed with time in a highly suggestive way, i.e., at 1-2 days, when mitotic activity was increased above normal, but low, 2n cells predominated; at 3 days, when mitotic rate was maximal, equal numbers of 2n and >2n cells were observed; and at 4-5 days, when mitotic rate dropped, the >2n cells were most evident. Culturing the hypertrophic cells (14 days of IPR treatment) produced only 2n cells. Measurements of nuclei of the enlarged cells, estimations of DNA content by visual examination, and the occurrence of polyploid cells in definite ratios with time all suggest the existence of polyploid nuclei in the enlarged glands.

Neural regulation of compensatory enlargement of the parotid gland of the rat.

SummaryThe role of the innervation in mediating compensatory enlargement of the parotid gland of the rat after partial desalivation was examined. The results of denervation experiments show that full compensatory growth requires both parasympathetic and sympathetic innervation. The presence of the parasympathetic innervation alone results in an increase in the number of cells, but not the size of the cells. The sympathetic innervation alone does not mediate either response. We, therefore, conclude that the two types of innervation have a synergistic action on the parotid to produce the maximal compensatory response, which includes an increase in both number and size of acinar cells.

Electrolyte Levels of Rat Salivary Secretions.

Summary Rat submaxillary-sublingual and parotid gland secretions, collected directly from salivary ducts for initial period of 3 minutes during stimulation by subcutaneously administered pilocarpine, exhibit patterns of sodium-potassium concentration that differ markedly from each other. Submaxillary-sublingual saliva is essentially hypo-osmotic to serum, with sodium concentration of 12 meq/1 and K of 53 meq/1, while parotid saliva has a total sodium-potassium concentration above that of serum (Na, 142 meq/1; K 18.5 meq/1). A broad correlation between gland sodium and potassium levels, together with changes on stimulation, and levels of these electrolytes in secretions from these glands is indicated.

Metrecal-Induced Changes in Human Saliva.

Summary A marked reduction in volume and total protein and amylase content of the secretion from the parotid gland of man occurred when young adult men were maintained for 7 days on a diet consisting exclusively of liquid Metrecal. Restriction of caloric intake (900 calories per day) caused a reduction in body weight of approximately 7 Ib per week when the diet was Metrecal or solid food; however, with the 900 calorie solid food diet, volume, amylase, or total protein of the secretion did not differ from those obtained from men maintained on an ad lib solid food diet. These changes in functional status of the parotid gland in man are attributed to a reduction in masticatory, and therefore, in the reflexly-mediated secretory stimuli to the gland. The submaxillary is not affected by the Metrecal treatment and a tentative explanation for these differences is presented.

Modification of the Action of Pilocarpine by Adrenergic Blocking Agents.

Summary Pilocarpine is not an equivalent substitute for parasympathetic nerve stimulation of the rat parotid gland when protein composition of the secretion is considered. Levels of amylase for example are appreciably higher with pilocarpine than with auriculo-temporal nerve stimulation. It has been found that Inderal, an agent which blocks adrenergic beta receptors, reduces amylase levels of pilocarpine-evoked saliva to levels observed with auriculo-temporal stimulation; on the other hand, Inderal does not modify amylase levels observed with auriculo-temporal stimulation. It is concluded that pilocarpine while having some actions that are parasympathomimetic has additional effects which involve stimulation of adrenergic receptor sites.

Mitosis Induced in Adult Rat Parotid Following Normal Activity of the Gland

Summary When normal function is restored by introduction of a solid food regimen to animals previously maintained on liquid diet (Metrecal) mitotic activity is induced, reaches a maximum after 2 days, (22 ± 2 per 1000 acinar cells), and remains evident until 7 days. The mitotic burst is partially inhibited in the presence of either atropine or Inderal. A decrease in DNA at 2 days followed by restoration to normal levels at 7 days suggests that, during the course of transition from low to normal functional status of the gland, cell loss must occur but is compensated for by the concurrently occurring cell proliferation. Normal physiological activity thus can act as the stimulus for inducing mitosis in the adult parotid where growth potential is low as well as in the immature parotid where growth potential is high. Glands of fasted rats exhibit similar mitotic bursts following refeeding with solid food, but not when they are refed using liquid food. A role of masticatory activity in this response is thus implied.