Inhibitory effects of substance P and carbachol on the saturable sodium-dependent uptake process of myo-inositol in rat parotid gland.
myo-Inositol uptake in prisms of rat parotid glands was investigated by measuring both the accumulation of free myo-[3H] inositol into the cytosol and its incorporation into phospholipids. Total myo-[3H]inositol uptake involved two distinct processes, a prominent one which is saturable and sodium-dependent (Km, 95 microM; Vmax, 8 pmol/mg of protein per min) and a minor one, nonsaturable and sodium-independent. Phloretin and cytochalasin B, two inhibitors of hexose transport, and D-glucose, but only at high concentrations (greater than 10 mM), inhibited myo-[3H]inositol uptake. Dixon plots of the data indicated that D-glucose inhibition was noncompetitive suggesting that myo-inositol and D-glucose are transported by different carriers. Electrogenic cotransport of sodium and myo-inositol, rather than energy derived from mitochondrial oxidative metabolism, seems to be involved in the transport process. Thus, ouabain, monensin or veratridine, all of which increase intracellular sodium concentrations, reduced myo-[3H]inositol uptake, whereas dinitrophenol, potassium cyanide and carbonyl cyanide m-chlorophenyl hydrazone were without effect. Substance P affected only the sodium-dependent uptake process of myo-[3H]inositol, this inhibitory effect requiring extracellular calcium. Similar observations were made with the muscarinic agonist carbachol. From these results, an increase in intracellular sodium concentration linked to the activation of calcium-sensitive cation-permeant channels appears to be responsible for the inhibitory effects of substance P and carbachol on myo-[3H]inositol uptake, these effects being mediated respectively by NK1 and muscarinic receptors coupled to a phospholipase C.
Torrens
Y
Y
Collège de France, Institut National de la Santé et de la Recherche Médicale U114, Paris, France.
Dietl
M
M
Beaujouan
J C
JC
Glowinski
J
J
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007294:Inositol / Q000493:pharmacokinetics*; D008297:Male; D010306:Parotid Gland / Q000378:metabolism*; D010693:Phloretin / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*; D013696:Temperature
D010743:Phospholipids; D013373:Substance P; D003571:Cytochalasin B; D007294:Inositol; D002217:Carbachol; D012964:Sodium; D005947:Glucose; D010693:Phloretin; D002118:Calcium