A novel function of thyrotropin as a potentiator of electrolyte secretion from the tracheal gland.
Accumulating evidence suggests that thyrotropin (thyroid-stimulating hormone [TSH]) plays some roles in immunoregulation by an extrathyroidal action. Because airway submucosal glands are responsible for nonspecific and specific airway defense, we tested the effect of TSH on feline tracheal submucosal gland using a whole-cell patch-clamp technique, immunohistochemistry, and reverse transcription/polymerase chain reaction (RT-PCR). TSH potentiated neurotransmitter-induced ionic currents significantly in a dose-dependent manner. Acetylcholine (10(-)(8) M)- and norepinephrine (10(-)(7) M)-induced inward current (I(i)), which we previously showed to be a Cl(-) current, were increased to about 3-fold the pre-TSH control responses, respectively, by 2.0 ng/ml TSH; and to 6- and 23-fold the control values by 20.0 ng/ml TSH, respectively. TSH alone was without effect up to 20.0 ng/ml. Follicular stimulating hormone only slightly affected the I(i) (1. 5-fold the control). Analyses with immunohistochemistry and RT-PCR failed to identify TSH receptors on the glandular tissue. Maneuvers to raise the cellular adenosine 3',5'-cyclic monophosphate also failed to mimic the TSH-mediated potentiation. The TSH effect appeared to be mediated by a signaling pathway involving tyrosine kinase because its inhibitors (genistein and herbimycin A) abolished the augmentation completely, and interferon-gamma, a tyrosine kinase activator, imitated the TSH action on submucosal gland. Thus, TSH may be an important regulator of airway fluid secretion.
Tamada
T
T
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Sasaki
T
T
Saitoh
H
H
Ohkawara
Y
Y
Irokawa
T
T
Sasamori
K
K
Oshiro
T
T
Tamura
G
G
Shimura
S
S
Shirato
K
K
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones; D002415:Cats; D000242:Cyclic AMP / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D007986:Luteinizing Hormone / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013972:Thyrotropin / Q000235:genetics / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*
D016227:Benzoquinones; D004573:Electrolytes; D047029:Lactams, Macrocyclic; D011809:Quinones; D012333:RNA, Messenger; D017828:Rifabutin; C020754:herbimycin; D007371:Interferon-gamma; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D019833:Genistein; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D007545:Isoproterenol; D000109:Acetylcholine; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine