The effect of a sympatho- and a parasympathomimetic drug on the electrolyte concentrations of primary and final saliva of the rat submaxillary gland

Ja, Young; Cj, Martin

doi:10.1007/bf00588449

Cited by 85 publications

(26 citation statements)

References 24 publications

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“…Salivary glands also secrete saliva in response to a β-adrenergic receptor-activated increase in intracellular cAMP. Unlike Ca 2+ -dependent salivation, little is known about the mechanism underlying the cAMP-dependent secretory process (19). It is unclear whether an increase in intracellular cAMP is sufficient to produce saliva, or whether cAMP exerts its secretory effect in a Ca 2+ -dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism underlying β-adrenergic-induced fluid secretion, including whether it is acinar and/or ductal in origin (19), is not well understood. One possibility is that β-adrenergic stimulation activates ion-transporting proteins shared with the muscarinicdependent pathway, including acinar Tmem16A channels.…”

Section: Ca 2+ -Dependent Fluid Secretion Is Abolished In Salivary Glmentioning

confidence: 99%

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A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland

Catalán

Kondo

Peña-Münzenmayer

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Activation of an apical Ca 2+ -activated Cl − channel (CaCC) triggers the secretion of saliva. It was previously demonstrated that CaCCmediated Cl − current and Cl − efflux are absent in the acinar cells of systemic Tmem16A (Tmem16A Cl − channel) null mice, but salivation was not assessed in fully developed glands because Tmem16A null mice die within a few days after birth. To test the role of Tmem16A in adult salivary glands, we generated conditional knockout mice lacking Tmem16A in acinar cells (Tmem16A −/− ). Ca 2+ -dependent salivation was abolished in Tmem16A −/− mice, demonstrating that Tmem16A is obligatory for Ca 2+ -mediated fluid secretion. However, the amount of saliva secreted by Tmem16A −/− mice in response to the β-adrenergic receptor agonist isoproterenol (IPR) was comparable to that seen in controls, indicating that Tmem16A does not significantly contribute to cAMP-induced secretion. Furthermore, IPR-stimulated secretion was unaffected in mice lacking Cftr (Cftr ΔF508/ΔF508 ) or ClC-2 (Clcn2 −/− ) Cl − channels. The time course for activation of IPR-stimulated fluid secretion closely correlated with that of the IPR-induced cell volume increase, suggesting that acinar swelling may activate a volume-sensitive Cl − channel. Indeed, Cl − channel blockers abolished fluid secretion, indicating that Cl − channel activity is critical for IPR-stimulated secretion. These data suggest that β-adrenergic-induced, cAMP-dependent fluid secretion involves a volume-regulated anion channel. In summary, our results using acinar-specific Tmem16A −/− mice identify Tmem16A as the Cl − channel essential for muscarinic, Ca 2+ -dependent fluid secretion in adult mouse salivary glands.acinar cell | secretion | Cl − channel | Tmem16A/Ano1 | Cftr channel

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Section: Discussionmentioning

confidence: 99%

Section: Ca 2+ -Dependent Fluid Secretion Is Abolished In Salivary Glmentioning

confidence: 99%

A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland

Catalán

Kondo

Peña-Münzenmayer

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Salivary sodium concentration although positively correlated with flow at most flow rates has been found to be negatively correlated to flow in a number of salivas when the flow rate is very low [Kay, 1960;Knauf and Fromter, 1970;Martin and Young, 1971;Young and Martin, 1971;Kaladelfos and Young, 1974]. This phenomenon has been explained as resulting from the saliva being able to re-equilibrate with the plasma at some region of the excurrent duct system due to the long transit time [Schneyer, Young and Schneyer, 1972].…”

Section: Discussionmentioning

confidence: 99%

Parotid Salivary Flow and Composition During Infusion of Acetylcholine and Atropine into the Carotid Artery of Conscious Sodium‐Replete Sheep

Beal

1979

Exp Physiol

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The rate of salivary flow and the concentrations of the major electrolytes in parotid saliva and arterial plasma of conscious sodium-replete sheep were measured during resting salivary secretion and when salivary flow was either increased by intracarotid infusion of acetylcholine at 10-30 nmol. min-' for 20 min or reduced by intracarotid infusion of atropine at 14 nmol. min-' for 50 min. During both treatments salivary phosphate concentration was always negatively correlated with salivary flow and salivary bicarbonate concentration was always positively correlated with flow. The chloride concentration of the saliva during the acetylcholine infusion experiments was positively correlated with salivary flow whereas when atropine was infused the chloride concentration was negatively correlated with flow. Acetylcholine infusion caused the potassium concentration of the saliva to increase significantly resulting in a marked increase in the total rate of loss of potassium in the saliva. The salivary potassium concentration fell significantly at the onset of atropine infusion and then rose progressively so that the potassium concentration was elevated by the end of the infusion. In both treatments the concentrations of sodium and hydrion were negatively correlated with salivary flow rate. The maximum sodium concentration which occurred in the low-flow saliva of the atropine infusion was substantially higher than the concentration that would be achieved by equilibrium with the aqueous phase of arterial plasma. It was concluded that the negative correlation between salivary flow and sodium concentration occurred because the reabsorption of sodium from the saliva by the excurrent duct system was minimal in sodium-replete sheep which would have low levels of mineralocorticoids in the circulation. The inconsistency between this study and previous reports presumably reflects differences in the criteria used to define the sodium status of the animals.During parasympathetic or parasympathomimetic stimulation of most salivary glands the sodium concentration of the saliva usually increases as the rate of flow increases so that over most of the flow range the concentration of sodium is positively correlated with the rate of salivary flow [Gregersen and Ingalls, 1931;Thaysen, Thorn and Schwartz, 1954;Brusilow and Cooke, 1959;Yoshimura, Iwasaki, Nishikawa and Matsumoto, 1959;Mangos and Braun, 1966; Petersen and Poulsen, 1967]. Most observations made on saliva from sheep salivary glands have agreed with this generalization. Coats and Wright [1957] found that after an initial transient fall the sodium concentration of parotid saliva increased as the salivary flow rate rose during electrical stimulation of the parotid nerve of anaesthetized sheep. A similar relation between sodium concentration and salivary flow has also been found in the submaxillary saliva of anaesthetized sheep during stimulation of the submaxillary nerve [Kay, 1960]. A positive correlation between parotid salivary flow and sodium concentration has been reported in...

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“…This approach, which has also been used in vivo, assumes that the composition of the primary saliva is constant, irrespective of the nature of the stimulus, so that the electrolyte composition of the final saliva reflects the activity of ductal transport processes. This assumption, which is based on micropuncture data in the rat mandibular gland (Young & Martin, 1971) seems all the more likely in the rabbit mandibular gland where, as we have seen, only acetylcholine evokes significant fluid secretion. Although indirect, this approach does allow the contribution of ducts other than the main duct to be evaluated.…”

Section: Electrolyte Secretionmentioning

confidence: 94%

Effects of acetylcholine, isoprenaline and forskolin on electrolyte and protein composition of rabbit mandibular saliva.

Case

Howorth

Padfield

1988

The Journal of Physiology

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SUMMARY1. The major purpose of this study was to investigate cellular regulation of the ductal transport processes in salivary glands which act to modify the electrolyte composition of primary saliva and cause it to become hypotonic. This was achieved using an isolated mandibular gland preparation by observing the effect of different stimuli on the electrolyte composition of saliva secreted at the same flow rate, on the assumption that these stimuli do not influence primary saliva composition. The effects of the same stimuli on the volume of primary fluid secretion and on protein secretion were also observed. Proteins were measured in total and as individual components after their separation by high-performance liquid chromatography.2. Acetylcholine was used as a 'Ca2+-mobilizing' agonist (i.e. one which both elevates intracellular Ca21 concentration and activates protein kinase C). Isoprenaline was initially used to elevate intracellular cyclic AMP concentration but was subsequently abandoned in favour of forskolin.3. Acetylcholine was a very potent stimulus of primary fluid secretion. By contrast, isoprenaline and forskolin were essentially without effect, even when superimposed on acetylcholine stimulation. 4. As judged by saliva electrolyte composition, increasing the concentration of acetylcholine enhanced ductal absorption of Na+ and Cl-and secretion of K+ (and presumably HCO3. Forskolin had the opposite effect: when superimposed on submaximal acetylcholine stimulation it caused saliva concentrations of Na+ and Cl-to remain high and K+ low (i.e. it inhibited ductal transport processes). The inhibitory effect of forskolin on ductal transport could be overcome by increasing the concentration of acetylcholine, and vice versa.5. Acetylcholine, isoprenaline and forskolin each increased salivary protein secretion, although the kinetics of secretion differed. The spectrum of proteins secreted in response to the three stimuli was the same. The relative proportions of the individual proteins was influenced by the strength of stimulation (i.e. the proportions at high total protein output differed from those at low total protein output) but not apparently by the nature of the stimulus.6. Thus, the three major secretory processes in the rabbit mandibular salivary gland respond differently to the two major signal transduction mechanisms. For R. M. CASE, A. J. HO WORTH AND P. J. PADFIELD primary fluid secretion, Ca2" is stimulatory and cyclic AMP almost without effect; for ductal transport, Ca2" is stimulatory and cyclic AMP inhibitory; and for protein secretion both Ca2+ and cyclic AMP are stimulatory.

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The effect of a sympatho- and a parasympathomimetic drug on the electrolyte concentrations of primary and final saliva of the rat submaxillary gland

Cited by 85 publications

References 24 publications

A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland

A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland

Parotid Salivary Flow and Composition During Infusion of Acetylcholine and Atropine into the Carotid Artery of Conscious Sodium‐Replete Sheep

Effects of acetylcholine, isoprenaline and forskolin on electrolyte and protein composition of rabbit mandibular saliva.

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