The effect of acetazolamide, amiloride, bumetanide and SITS on secretion of fluid and electrolytes by the parotid gland of common wombats, Vombatus ursinus. 2021

A M Beal
School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, 2052, Australia. a.beal@unsw.edu.au.

Mechanisms of saliva formation by wombat parotid glands were investigated in anaesthetized wombats at two levels of cholinergically-stimulated flow viz. mid-range (30-40% maximum flow) and maximum flow using ion-transport and carbonic-anhydrase inhibitors. Bumetanide (0.005-0.1 mmol l-1 carotid plasma) progressively reduced mid-range flow by 52 ± 3.4% (mean ± SEM). Concurrently, saliva [Cl] decreased, [Na] and [HCO3] increased but HCO3 excretion was unaltered. Salivary flow during high-rate cholinergic stimulation was 31 ± 1.1% of the pre-bumetanide maximum. During mid-range stimulation, SITS (0.075 mmol l-1) was without effect whereas 0.75 mmol l-1 stimulated transient increases in fluid output. The higher SITS concentration caused no alterations to flow or electrolyte concentrations during maximal stimulation. Carotid plasma [amiloride] (0.05 mmol l-1) caused immediate falls in flow rate of 20-30% followed by progressive recovery over 25 min to levels above pre-amiloride flow rates despite plasma [amiloride] increasing tenfold. Concurrently, salivary [Na] and [Cl] rose to equal plasma concentrations and [K] fell by 50% indicating blockade of acinar Na/H exchangers and luminal Na channels in the ducts. Increased salivary osmolarity caused the flow recovery. Saliva flow during maximum cholinergic stimulation was reduced by 38-46%. The depression of flow was interpreted as resulting from competition between amiloride and acetylcholine for access to the muscarinic receptors. Plasma [acetazolamide] (0.35-2.5 mmol l-1) did not alter saliva outflow during mid-range or maximum flow regimes whereas salivary [Cl] increased and [HCO3] decreased consistent with reduced anion exchange resulting from inhibition of carbonic anhydrase. Combined with bumetanide, acetazolamide (1.5 mmol l-1) reduced flow by an additional 18-22% relative to bumetanide alone thereby demonstrating that acinar HCO3 synthesis supported a limited proportion of saliva formation and that some HCO3 secretion was independent of carbonic anhydrase activity.

UI MeSH Term Description Entries
D010306 Parotid Gland The largest of the three pairs of SALIVARY GLANDS. They lie on the sides of the FACE immediately below and in front of the EAR. Gland, Parotid,Glands, Parotid,Parotid Glands
D002034 Bumetanide A sulfamyl diuretic. Bumedyl,Bumethanide,Bumex,Burinex,Drenural,Fordiuran,Miccil,PF-1593,PF 1593,PF1593
D002712 Chlorides Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D004573 Electrolytes Substances that dissociate into two or more ions, to some extent, in water. Solutions of electrolytes thus conduct an electric current and can be decomposed by it (ELECTROLYSIS). (Grant & Hackh's Chemical Dictionary, 5th ed) Electrolyte
D000086 Acetazolamide One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337) Acetadiazol,Acetazolam,Acetazolamide Sodium, (Sterile),Acetazolamide, Monosodium Salt,Ak-Zol,Apo-Acetazolamide,Diacarb,Diamox,Diuramide,Défiltran,Edemox,Glauconox,Glaupax,Huma-Zolamide,Ak Zol,AkZol,Apo Acetazolamide,ApoAcetazolamide,Huma Zolamide,HumaZolamide
D000584 Amiloride A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705) Amidal,Amiduret Trom,Amiloberag,Amiloride Hydrochloride,Amiloride Hydrochloride, Anhydrous,Kaluril,Midamor,Midoride,Modamide,Anhydrous Amiloride Hydrochloride,Hydrochloride, Amiloride,Hydrochloride, Anhydrous Amiloride,Trom, Amiduret
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001639 Bicarbonates Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the pH of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Bicarbonate,Bicarbonate Ions,Hydrogen Carbonates,Bicarbonate Ion,Carbonic Acid Ions,Hydrogen Carbonate,Carbonate, Hydrogen,Carbonates, Hydrogen,Ion, Bicarbonate,Ions, Bicarbonate,Ions, Carbonic Acid
D012469 Salivary Glands Glands that secrete SALIVA in the MOUTH. There are three pairs of salivary glands (PAROTID GLAND; SUBLINGUAL GLAND; SUBMANDIBULAR GLAND). Gland, Salivary,Glands, Salivary,Salivary Gland

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