Colchicine analogues that bind reversibly to tubulin define microtubular requirements for newly synthesized protein secretion in rat lacrimal gland.
The role of microtubules in 3H-labeled protein secretion in rat lacrimal glands was probed by the use of colchicine and two of its analogues that reversibly bind to tubulin. These analogues were 2-methoxy-5-(2,3,4,4'-trimethoxyphenyl)-2,4,6-cycloheptatriene-1-o ne and 2,3,4,4'-tetramethoxy-1,1'-biphenyl, the latter having been synthesized for these studies. Immunofluorescence revealed that untreated exocrine acinar cells contained an intact microtubule network, which was totally abolished by drug addition. Subsequent drug removal restored the network for the two reversibly binding drugs--more rapidly so for the biphenyl, but this was not the case with colchicine. The protein-secretory process was examined by adding the three drugs at various stages--prepulse incubation, pulse, maturation, apical storage of granules, and discharge under cholinergic stimulation. Comparison with the kinetics of microtubular network restoration, which differed for the two reversibly binding drugs, led to the conclusion that the microtubular system is critical to the maturation phase of secretion.
Herman
G
G
Laboratoire de Biochimie des Transports Cellulaires, Centre National de la Recherche Scientifique UA 1116, Université de Paris-Sud, France.
Busson
S
S
Gorbunoff
M J
MJ
Mauduit
P
P
Timasheff
S N
SN
Rossignol
B
B
D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism* / Q000494:pharmacology; D003078:Colchicine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D003508:Cycloheptanes / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007700:Kinetics; D007765:Lacrimal Apparatus / Q000378:metabolism*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014334:Tropolone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism / Q000502:physiology*
D001713:Biphenyl Compounds; D003508:Cycloheptanes; D011506:Proteins; D014404:Tubulin; C030370:2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone; C060033:2,3,4,4'-tetramethoxy-1,1'-biphenyl; D014334:Tropolone; D003078:Colchicine