The influence of sympathomimetic and sympatholytic agents on the salivary flow rate and concentration of Ca, P and protein in the parotid gland of the goat

1. The role of the sympathetic autonomic division on the parotid gland of normal and thyroparathyroidectomized (t.x.p.t.x.) goats was studied. 2. The salivary flow rate and concentration of Ca, P and protein was tested during the intravenous infusions of sympathomimetic and sympatholytic agents. 3. The intravenous infusion of isoprenaline modified the salivary flow rate and the concentration of total protein. 4. None of the tested drugs modified significantly the concentration of Ca and P in the parotid saliva. 5. The results obtained in normal and t.x.p.t.x animals were similar; it seems that PTH is not involved in the observed changes.     

The effects of intravenous phosphate loading on salivary phosphate secretion and plasma parathyroid hormone levels in the sheep.

Adult sheep were given intravenous infusions of a solution of Na2HPO4 and the effects on parotid salivary composition and on plasma parathyroid hormone levels were studied. Infusion of the phosphate solution resulted in increases in the concentration of inorganic phosphate in the plasma and to proportional increases in the concentration and amount of phosphate secreted in the saliva. There was, however, no evidence that the salivary response was dependent upon a change in endogenous parathyroid hormone release. In other studies infusion of bovine parathyroid hormone or stimulation of endogenous hormone release through infusion of EDTA both led to a fall in the concentration of inorganic phosphate in the plasma and to a fall in the concentration and amount of phosphate secreted in the saliva. Taken together these results suggest that the major factor affecting salivary phosphate secretion in these studies was the concentration of inorganic phosphate in the plasma. Parathyroid hormone does not appear to have any direct effect on salivary phosphate secretion in the sheep though it may indirectly influence phosphate secretion through its effects on plasma inorganic phosphate level.     

The role of the autonomic nervous system in the depression of parotid salivary secretion during hyperkalaemia in conscious sheep.

The rate of flow and electrolyte concentration of parotid saliva were measured before, during and after intravenous and contralateral intracarotid infusion of KCl (0.5 mol.1(-1)) and NaCl (0.5 mol.1(-1)) at 385-625 mumol. min(-1) for 40 min into 5 sheep. In intact conscious sheep contralateral intracarotid infusion of KCl caused marked depression of salivary secretion in all experiments whereas infusion of NaCl had no consistent effect on flow. Intravenous infusion of KCl into the intact conscious sheep caused a slight depression of salivary secretion but minimum flow was significantly higher than that during intracarotid infusion. When the sheep were anaesthetized salivary flow rates were low and contralateral intracarotid infusion of KCl either had no effect on flow or caused an increase in flow. After ipsilateral cervical sympathectomy contralateral intracarotid infusion of KCl into the conscious sheep caused a marked depression of salivary flow similar to that occurring when the sheep were intact. After section of the secretomotor nerve of the gland salivary flow rates were low and contralateral intracarotid infusion of KC1 had no effect on flow. The salivary flow responses of the sheep were consistent, regardless of whether the KCl infusions were given within 24 h or 1-2 weeks after cervical sympathectomy or secretomotor nerve section. Salivary sodium concentration was negatively correlated with salivary flow in all experiments. It was concluded that potassium acted at a site located in the head but by direct action on the salivary gland. The depression of salivary secretion by hyperkalaemia resulted from a decline in neural activity in the parasympathetic secretomotor innervation of the parotid gland.     

Intact and carboxyterminal PTH do not cross the blood-cerebrospinal fluid barrier

In order to examine whether parathyroid hormone (PTH) enters the cerebrospinal fluid (CSF), the blood levels of the hormone were acutely elevated either by infusion of parathyroid extract or by stimulation of the parathyroid glands by hypocalcemia. Despite marked elevations in the blood levels of the hormone, PTH could not be detected in the CSF. The data indicate the intact PTH or its carboxyterminal fragment do not cross the blood-CSF interface of the blood-brain barrier. The results, therefore, suggest that the action of PTH on brain must be mediated by an effect on the blood-brain interface of the blood-brain barrier.     

Parathyroid responsiveness to hypocalcemic and hypercalcemic stimuli in adult growth hormone deficiency after growth hormone replacement

Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Previous reports have suggested that alterations in parathyroid gland responsiveness to changes in calcium concentration may play a role in the genesis of osteoporosis in untreated AGHD patients. We investigated the endogenous parathyroid hormone [PTH-(1-84)] response to hypocalcemic and hypercalcemic stimuli induced by sodium EDTA and calcium gluconate infusion, respectively, and to PTH-(1-34) infusion in AGHD patients before and during GH replacement (GHR). We have demonstrated that the maximum PTH-(1-84) stimulation and suppression occurred at significantly higher calcium concentrations and in response to smaller changes in calcium concentrations after GHR. The calcemic response to the effects of PTH-(1-34) infusion significantly increased after GHR. The calcium set point (the calcium concentration at which the rate of PTH secretion is one-half of its maximal value) significantly increased in all groups after 3 mo on GHR, and it increased further at 12 mo. Our results suggest increased parathyroid gland sensitivity to smaller changes in serum calcium and increased end-organ sensitivity to the effects of PTH in AGHD patients after GHR. These findings may help us to understand the mechanisms underlying the genesis of osteoporosis in AGHD patients.     

Modulating effects of prostaglandins on parasympathetic-mediated secretory activities of rat salivary glands

Exogenously administered PGE1 or PGE2, like atropine, markedly decreased both the flow and calcium concentration of parasympathetically evoked rat parotid saliva; PGF2 alpha was less effective. Despite the fact that prostaglandins greatly reduced the Ca concentration of nerve-evoked saliva, they did not change the glandular Ca concentration of either control or parasympathetically stimulated parotid glands. Prostaglandins (20 micrograms/kg, i.a.) decreased the Na or K concentration of nerve-evoked parotid saliva, but at lower doses had no significant effect. PGE1, PGE2, PGF2 alpha or atropine markedly decreased flow rates of similarly evoked rat submandibular saliva. Prostaglandins and atropine, however, decreased the Na concentration and increased the K concentration of parasympathetically evoked submandibular saliva. PGF2 alpha, like atropine, increased the Ca concentration of such saliva. Drug vehicle, ethanol, slightly decreased the flow of both parotid and submandibular saliva but not the ion secretion, Endogenous prostaglandins themselves may not play a role in secretory activities during parasympathetic nerve stimulation of rat salivary glands, since administration of indomethacin, and inhibitor of prostaglandin biosynthesis, prior to or during nerve stimulation did not significantly alter nerve-evoked salivary secretion, The mechanisms by which prostaglandins modulate secretory responses of salivary glands during parasympathetic stimulation are not understood.     

A functional and chemical study of radiation effects on rat parotid and submandibular/sublingual glands.

The aim of this study was to monitor composition and rate of secretion of rat parotid and submandibular/sublingual saliva following local single doses of X-rays ranging from 5 to 20 Gy. Pilocarpine-stimulated samples of parotid and submandibular/sublingual saliva were simultaneously collected with miniaturized Lashley cups before and 1-30 days after irradiation. The lag phase (period between injection of pilocarpine and start of the secretion) and flow rate were recorded and the concentrations of sodium, potassium, calcium, phosphate, and amylase were measured. With increasing dose and time, the salivary flow rate as well as sodium concentration decreased, while potassium concentrations increased throughout the follow-up period. The lag phase and the concentration of amylase reached their maximum at 3 and 10 days after irradiation, respectively. The changes in lag phase and flow rate were most obvious after doses of 15 or 20 Gy and showed a great similarity for parotid and submandibular/sublingual saliva. No dose-response relationship was observed for the changes in concentrations of calcium and phosphate. It is concluded that for radiation doses of 10 Gy and above, irreversible changes (lag phase, flow rate, potassium, sodium) were observed. A saturation of the irradiation effects (lag phase, flow rate) seems to exist at doses larger than 15 Gy. No significant differences were observed between the radiation-induced functional changes in parotid and submandibular/sublingual salivary gland tissue.     

Age, strain and species differences in circulating parathyroid hormone

A new, sensitive parathyroid hormone (PTH) radioimmunoassay that appears specific for the intact hormone, and its validation for measuring rat PTH are described. The assay is based on antibody C2-7 from chicken immunized with bovine PTH; it has a detection limit of 6 pg of bPTH per assay tube and measures basal PTH in most rats; it is responsive to provoked changes in endogenous PTH concentration, and the intra-assay and inter-assay coefficients of variation are 6.0% and 7.2%, respectively. Multiple dilutions of rat serum and parathyroid gland extract, result in competitive inhibition curves that are parallel to that of highly purified bPTH. Under our assay conditions the C2-7 antibody cross-reacts well with intact PTH but synthetic fragments of the hormone (1-34bPTH, 1-34hPTH, 28-48hPTH, 44-68hPTH, 53-84hPTH) do not depress tracer (125l-bPTH) binding to the antibody. Studies designed to validate the assay gave predictable results such as enhanced secretion of the hormone in response to EDTA infusion, and failure to detect the hormone in serum following thyroparathyroidectomy. In addition, we made the novel observation that in F344 rats circulating immunoreactive PTH increases progressively with aging.     

Serum osteocalcin levels do not change during rapidly induced hypercalcemia in healthy subjects.

Since osteocalcin has been suggested to play a role in calcium homeostasis, we investigated its serum levels in 6 healthy subjects during a rapid calcium infusion. Serum levels of intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25-(OH) D3] and 1,25-dihydroxyvitamin D [1,25-(OH)2 D3] were also determined. The calcium infusion increased plasma-ionized calcium levels from 1.25 +/- 0.04 to 1.54 +/- 0.07 mmol/l at 30 min (p less than 0.05). Concomitantly, serum levels of intact PTH declined from 2.1 +/- 0.9 to 0.2 +/- 0.3 mmol/l (p less than 0.05). In contrast, serum osteocalcin levels did not change. Further, during calcium infusion, serum levels of 1,25-(OH)2 D3 decreased from 81 +/- 17 to 75 +/- 15 pmol/l (p less than 0.05) whereas serum levels of 25-(OH) D3 did not change. The results therefore suggest that calcium per se does not influence osteocalcin secretion.     

Modulating effects of prostaglandins on parasympathetic-mediated secretory activities of rat salivary glands

Exogenously administered PGE₁ or PGE₂, like atropine, markedly decreased both the flow and calcium concentration of parasympathetically evoked rat parotid saliva: PGF_2α was less effective. Despite the fact that prostaglandins greatly reduced the Ca concentration of nerve-evoked saliva, they did not change the glandular Ca concentration of either control or parasympathetically stimulated parotid glands. Prostaglandins (20 μg/kg, i.a.) decreased the Na or K concentration of nerve-evoked parotid saliva, but at lower doses had no significant effect. PGE₁, PGE₂, PGF_2α or atropine markedly decreased flow rates of similarly evoked rat submandibular saliva. Prostaglandins and atropine, however, decreased the Na concentration and increased the K concentration of parasympathetically evoked submandibular saliva. PGF_2α, like atropine, increased the Ca concentration of such saliva. Drug vehicle, ethanol, slightly decreased the flow of both parotid and submandibular saliva but not the ion secretion. Endogenous prostaglandins themselves may not play a role in a secretory activities during parasympathetic nerve stimulation of rat salivary glands, since administration of indomethacin, an inhibitor of prostaglandins biosynthesis, prior to or during nerve stimulation did not significantly alter nerve-evoked salivary secretion. The mechanisms by which prostaglandins modulate secretory responses of salivary glands during parasympathetic stimulation are not understood.     

Plasma parathyroid hormone during acute volume expansion in the rat

Various studies have suggested the possibility that volume expansion may increase parathyroid hormone (PTH) secretion. PTH appears to have renal effects consistent with the actions of a natriuretic and diuretic and the possibility exists that PTH may play a physiological role in volume homeostasis. The present studies were designed to examine whether PTH levels in plasma from rats was influenced by acute volume expansion and whether such effects were independent of alterations in plasma ionized calcium concentration. Volume expansion with calcium-free bicarbonate Ringers (10% of body weight, IV) led to a drop in plasma ionized calcium from 1.08 to 0.92 mMol/l (p less than 0.01) while plasma PTH concentration was increased from 67.2 to 114.2 pMol/l. Volume expansion with bicarbonate Ringers solution (also 10% of body wt, IV) which contained 1.8 mM CaCl2 was not associated with any significant change in either plasma ionized calcium or plasma PTH concentration. However, measurements of blood packed cell volume (PCV) revealed that infusion resulted in a drop in PCV from 49.7 to 41.1% (p less than 0.01). This represents a dilution of plasma of approximately 42%. The absence of any drop in plasma PTH during isocalcemic volume expansion suggests an underlying stimulus to PTH secretion during volume expansion independent of plasma ionized calcium levels.     

The composition and flow of parotid saliva during acute hyperkalaemia in sodium-deficient sheep.

Sheep were infused intravenously with 0-43 M-KCl at 2 ml/min for 2 hr while they were either sodium-replete or sodium-deficient after the unilateral loss of parotid saliva for 18 hr or 3 days. Salivary flow was depressed during potassium infusion and the flow rates observed at maximum hyperkalaemia were similar in all three states of sodium balance despite the large differences in flow rate before potassium infusion. The fall in salivary Na/K ratio during potassium administration was diphasic, the initial decline being slow and followed by a more rapid fall in the ratio. The duration of the initial period of slow decline in this ratio ranged from 75-105 min, 45-60 min, and about 15 min in the sodium-replete, mildly sodium-deficient and severely sodium-deficient states respectively. The decline in salivary flow during sodium depletion was associated with decreasing salivary bicarbonate concentration and increasing salivary phosphate and hydrogen ion concentrations with the concentration of chloride showing no consistent trend. During acute hyperkalaemia the chloride and phosphate concentrations were negatively correlated with salivary flow, the bicarbonate concentration was positively correlated with flow and the hydrogen ion concentration was unaltered. The sodium concentration of the saliva showed a statistically significant correlation with flow only when the sheep were severely sodium-deficient.     

Interactions between sodium and calcium intake and blood pressure responses to norepinephrine and parathyroid hormone

The present study has examined the vascular responses to infusion of norepinephrine (NE) and parathyroid hormone (PTH 1-34) in animals subjected for a six month period to one of four dietary regimens. Some animals received normal calcium chow (1.0% Ca by weight) and drank water (subgroup A), others consumed the same chow, but water was replaced by 0.5% saline (subgroup B), a third group consumed chow which had 2.0% Ca content and also drank 0.5% saline (subgroup C) and a fourth group consumed the 2.0% Ca chow, but drank water (subgroup D). No differences were found in the pressor response to NE across subgroup A, B, and C, while pressor response to NE in subgroup D was markedly reduced. Depressor responses to PTH were not significantly different across any of the four groups. The ability of changes in calcium homeostasis to affect blood pressure responses to NE and PTH were evaluated in animals consuming reduced dietary calcium (0.1%) for two and four weeks and compared with animals on normal calcium intake (1.0%). This dietary treatment resulted in only mild effects on calcium balance; after four weeks no significant difference in plasma total calcium concentration was observed, but plasma PTH levels were increased in animals on the low Ca diet. No effects on the blood pressure response to NE or PTH infusion were observed after 2 weeks of dietary treatment. At four weeks, NE responses remained unchanged, while responses to PTH were blunted in animals on 0.1% Ca chow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of ruminal and plasma osmotic pressure on salivary secretion in sheep

The osmotic pressure of the rumen contents and also of the blood was altered by intraruminal administration of water or hypertonic solutions. It was found that alterations in osmotic pressure were accompanied by inverse changes in the flow rate of mixed saliva. Intravenous infusion of hypertonic solutions, causing elevation of the osmotic pressure of the blood without affecting that of the rumen, also caused a reduction of salivary secretion rate. The flow rates of both parotid and residual saliva were affected. When strongly hypertonic solutions of sodium or potassium salts were infused into the rumen, or sodium salts or urea were infused into the blood, the concentration of those substances increased in the saliva. Other treatments had little effect on salivary composition.     

Serum intact parathyroid hormone concentration measured by a two-site immunoradiometric assay in normal subjects and patients with various parathyroid disorders.

Serum intact parathyroid hormone (PTH) concentration was measured by a two-site immunoradiometric assay (IRMA) in normal subjects and patients with various parathyroid disorders. Serum intact PTH levels were all within the detection limit of the IRMA in normal subjects, and there was a significant negative correlation between serum calcium (Ca) and intact PTH levels. Although 3 out of 26 patients (11.5%) with primary hyperparathyroidism had a normal serum intact PTH concentration, these patients could be readily discriminated from normal subjects by plotting serum intact PTH against the serum Ca concentration. In contrast, serum intact PTH was undetectable in 16 out of 17 patients (94.1%) with idiopathic hypoparathyroidism. Patients with pseudohypoparathyroidism (PHP) type I, mostly under treatment with active vitamin D, exhibited wide distribution of serum intact PTH concentration, and appeared to belong to two distinct subgroups. One group of patients demonstrated a similar relationship between serum intact PTH and Ca levels to normal subjects. The other exhibited much higher serum intact PTH levels despite a normal serum Ca concentration, and no obvious relationship could be observed between the two parameters. These results demonstrate that an inverse relationship between serum Ca and intact PTH can be demonstrated in normal subjects with normocalcemia, that most of the parathyroid disorders can be diagnosed by measuring serum Ca and the intact PTH concentrations simultaneously, and that patients with PHP can be divided into two subgroups: one with a normal relationship between serum Ca and intact PTH, and the other with a high serum PTH level in the face of normocalcemia.     

Suppression of secondary hyperparathyroidism in uraemia: acute and chronic studies.

A study was conducted evaluating the response of serum parathyroid hormone to acute hypercalcaemia and long term administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in patients receiving maintenance haemodialysis. During infusion of elemental calcium 4 mg/kg/h over four hours in 12 patients not receiving vitamin D the concentration of serum amino terminal parathyroid hormone fell by 31-96% (mean 74.8 (SD 17.6)%) while that of carboxy terminal parathyroid hormone changed little. There was a strong inverse correlation between baseline serum calcium concentration and percentage fall in amino terminal parathyroid hormone during infusion (r = 0.88; p less than 0.001). In seven patients who received prolonged treatment with 1,25(OH)2D3 after calcium infusion there was a positive correlation between maximum percentage fall in amino terminal parathyroid hormone during infusion and the percentage fall in amino terminal parathyroid hormone after 1,25(OH)2D3 treatment (r = 0.79; p less than 0.05). The responsiveness of the parathyroid glands to changes in calcium in acute studies may be used to predict the efficacy of long term treatment with 1,25(OH)2D3. Patients in whom calcium infusion does not suppress parathyroid hormone may have true parathyroid autonomy and require early parathyroidectomy.     

Effects of parathyroid hormone on exocrine pancreatic secretion in parathyroidectomized dogs

The effects of intravenous parathyroid hormone (PTH) on steady state Secretin-induced pancreatic secretion were studied in seven dogs before and after parathyroidectomy. Free flow of pancreatic juice was obtained by direct cannulation of the main pancreatic duct (the minor duct being ligated) : a gastric fistula prevented the entry of gastric acid into the duodenum. In the normal dog PTH caused a significant increase in volume and bicarbonate concentration, reciprocal change in chloride and no change in total protein concentration. The stimulatory effect of PTH was dose-dependent. In the parathyroidectomized dog, the basic Secretin-induced secretion was lower than the preoperative values, but PTH infusion caused a significant increase in volume of fluids and bicarbonate concentration, reciprocal change in chloride and no change in protein concentration. These results were not dependent on calcium blood level, and did not change after calcium injection to the hypocalcemic parathyroidectomized dog. It is suggested, that PTH may have a direct effect on pancreatic exocrine secretion.     

Some Acute Metabolic Effects of Parathyroid Hormone in Sheep

PERSSON, J. and J. LUTHMAN: Some acute metabolic effects of parathyroid hormone in sheep. Acta vet. scand. 1974, 15, 381–397. — It is now well established that calcium ions play a key role in the activation of many different cell systems. Parathyroid hormone (PTH) causes a shift of calcium into bone cells, and lipolytic hormones have little or no effect in calcium-free media. In the present investigation sheep were used to study the acute effects of intravenous injection of bovine PTH on mineral and lipid metabolism. A significant initial hypocalcaemia was found in all groups of animals. The subsequent rise in plasma calcium was most pronounced in rams. Thyroid-ectomized animals showed a greater calcium response than did intacts. PTH was found to have a strong lipolytic effect, comparable to that of catecholamines, and a slight hyperglycaemic effect. The rise in plasma NEFA was blocked by nicotinic acid, while the hyper-glycaemia was potentiated. Hypophosphataemia was obtained in young rams but not in young ewes, and in elder ewes a slight increase in the plasma phosphate level was found. Plasma magnesium decreased in all groups after PTH injection, while PTH + nicotinic acid caused a rise in magnesium concentration. The results are discussed in the view of current knowledge of mineral and lipid metabolism. parathyroid hormone; hypocalcaemia; lipolysis; sheep.     

A comparative study of salivary secretion by parotid and mandibular glands of anaesthetized Capra hircus: effect of pilocarpine

A study was made of basal secretion and the effect of the infusion of pilocarpine on the flow and composition of saliva in the parotid and mandibular glands of the anaesthetized lactating goat. In the parotid gland there was a basal flow (1.6 +/- 0.29 microliter/min) which was not present in the mandibular gland. There is a statistically significant dose-effect relationship between pilocarpine and salivary flow in both glands. Salival composition and its variation with respect to the flow of saliva did not conform to either of the two glands to an exclusive monogastric or ruminant model.     

Effects of chronic clonidine administration on parasympathetic-evoked rat saliva.

Effects of chronic administration of clonidine on parasympathetic-evoked saliva from both parotid and submandibular glands were investigated. Clonidine at 1 mg/kg/day for 5 or 7 days caused a significant reduction in the salivary secretion (flow rate and total volume) evoked by parasympathetic nerve stimulation of parotid but not submandibular glands. Ion concentrations (Na, K and Ca) of parasympathetically nerve-evoked parotid saliva were not altered. However, the total protein concentration as well as output, amylase activity, and output of such saliva were markedly increased. Possible mechanisms for clonidine-induced increase in nerve-elicited salivary protein concentration include release of neuropeptides, and changes in adrenergic receptor binding which need further study.