title: Differential effects of cytoskeletal agents on hemispheric functional expression of cell membrane receptors in Xenopus oocytes.
abstract: 1. We studied the effects of three cytoskeleton-disrupting agents, colchicine (COL), vinblastine (VIN), cytochalasins, on the functional hemispheric expression of native muscarinic and acquired thyrotropin-releasing hormone receptors TRH-Rs). Responses in oocytes of common donors, which express M3-like receptors (M3Rs), were not affected by either COL or VIN on the animal hemisphere. The functional expression of M3Rs on the vegetal hemisphere was inhibited by 50%. Cytochalasin B caused a uniform inhibition (by 31-33%) of receptor functional expression on either hemisphere. 2. Oocytes of variant donors express predominantly M1-like receptors (M1Rs) on the animal and M3Rs on the vegetal hemisphere. In these oocytes, both COL and VIN caused approximately 50% inhibition of functional expression on either hemisphere. Cytochalasin B caused more extensive, though variable inhibition on both hemispheres. Both antitubulin agents had no effect on the functional expression of the TRH-Rs on either hemisphere. Cytochalasin B, however, caused an extensive inhibition of the functional expression of this receptor (by 70-75%). 3. Induction of maturation of oocytes (7-hr incubation with progesterone) resulted in a 66% decrease in the response to TRH, reflecting mainly a decrease on the animal hemisphere. Maturation in the presence of colchicine had no further effect on the activity measured on the animal hemisphere but caused a major increase in the activity on the vegetal hemisphere. This resulted in a dramatic change in animal/vegetal activity ratio (4.8 +/- 1.5 to 0.8 +/- 0.2). 4. It appears that while antitubulin drugs affect the functional expression of the three receptors at the two hemispheres differently, disruption of the microfilaments interferes uniformly with receptor functional expression. We suggest that microfilaments may be involved in a common component of the signal transduction pathway in oocytes or in the anchoring of receptors coupled to the guaninine nucleotide-binding regulatory proteins. Moreover, progesterone-induced changes in the functional organization of the signal transduction pathway appear to be controlled to a large extent by the tubulin component of the cytoskeleton.
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Matus-Leibovitch
authors.forename: M C
authors.initials: MC
authors.lastname: Gershengorn
authors.forename: Y
authors.initials: Y
authors.lastname: Oron
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D003078:Colchicine / Q000494:pharmacology*; D003572:Cytochalasins / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010911:Pituitary Neoplasms; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000096:biosynthesis* / Q000187:drug effects; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000096:biosynthesis* / Q000187:drug effects; D050257:Tubulin Modulators; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology*; D014981:Xenopus
chemical_list: D000596:Amino Acids; D003572:Cytochalasins; D011956:Receptors, Cell Surface; D011976:Receptors, Muscarinic; D018025:Receptors, Thyrotropin-Releasing Hormone; D050257:Tubulin Modulators; D011374:Progesterone; D014747:Vinblastine; D003078:Colchicine