A stimulatory role of protein kinase C in feline tracheal submucosal gland secretion.
To determine the role of protein kinase C (PKC) in airway submucosal gland secretion, we examined the effect of a selective PKC stimulant, phorbol 12-myristate 13-acetate (PMA), on mucus glycoprotein (MGP) secretion, fluid secretion and intracellular Ca2+ concentration ([Ca2+]i) in isolated feline submucosal glands. MGP and fluid secretions were estimated by measuring trichloroacetic acid (TCA)-precipitable glycoconjugates and 22Na-efflux, respectively, from isolated glands. [Ca2+]i was measured using a Ca(2+)-sensitive fluorescent dye, Fura 2. PMA itself produced a significant increase in MGP secretion in a dose-dependent fashion (173% of control at 10(-5) M). PMA also produced a significant increase in 22Na-efflux (151% of baseline rate constant at 10(-5) M). Indomethacin failed to alter the increase in MGP secretion or in 22Na-efflux in response to PMA. Two PKC inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and sphingosine, inhibited both MGP secretion and 22Na-efflux stimulated by PMA; there was only a partial inhibition after stimulation by methacholine (MCh). PMA did not significantly alter [Ca2+]i and H-7 did not alter the MCh-induced [Ca2+]i rise. These findings indicate that PKC has a direct stimulatory role in stimulus-secretion coupling of airway submucosal gland secretion.
Shimura
S
S
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ishihara
H
H
Nagaki
M
M
Sasaki
H
H
Takishima
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002415:Cats; D006001:Glycoconjugates / Q000032:analysis / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D009092:Mucous Membrane / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D012964:Sodium / Q000378:metabolism; D012979:Sodium Radioisotopes; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014132:Trachea / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D014316:Tritium
D006001:Glycoconjugates; D006023:Glycoproteins; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D012979:Sodium Radioisotopes; C047874:gastric mucus glycoproteins; D016210:Methacholine Chloride; D014316:Tritium; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D011493:Protein Kinase C; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium