Thymopoietin, a thymic polypeptide, prevents nicotinic agonist-induced morphological changes in neonatal muscle cells in culture.
Thymopoietin, a polypeptide hormone isolated from thymus and involved in immune function, potently inhibited [125I]alpha-bungarotoxin binding to neonatal muscle cells in culture (IC50 = 3.8 nM) and blocked carbachol-stimulated 22Na uptake with an IC50 of 1.9 +/- 0.2 nM and 23 +/- 7 nM at a half-maximal and maximal concentration of carbachol, respectively. Studies were subsequently done to evaluate potential long-term functional consequences of this interaction of thymopoietin at the nicotinic receptor. Exposure (1-3 days) of neonatal muscle cells in culture to nicotine (3 x 10(-6) M) or carbachol (1 x 10(-6) M) resulted in a decline in myotube branching and a decrease in myotube length. Thymopoietin did not appreciably alter myotube morphology on its own; however, it prevented the effects of nicotine and carbachol on muscle cell morphology at concentrations (1-10 nM) which corresponded well to those with which thymopoietin interacted at the receptor. The action of alpha-bungarotoxin on the myotubes was very similar to that of thymopoietin. These studies suggest that the endogenously occurring polypeptide, thymopoietin, has the potential to modulate muscle cell morphology through an interaction at the nicotinic receptor.
Quik
M
M
Department of Pharmacology, McGill University, Montreal, Que., Canada.
Philie
J
J
Goldstein
G
G
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002038:Bungarotoxins / Q000378:metabolism* / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D009132:Muscles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D013946:Thymopoietins / Q000494:pharmacology*; D014403:Tubocurarine / Q000494:pharmacology
D002038:Bungarotoxins; D011978:Receptors, Nicotinic; D013946:Thymopoietins; D009538:Nicotine; C032841:thymopoietin III; D002217:Carbachol; D012964:Sodium; D014403:Tubocurarine