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Apparent up-regulation of stimulatory G-protein subunits in the pregnant human myometrium is mimicked by elevated smoothelin expression, ¹

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Abteilung für Pharmakologie, Universitäts-Krankenhaus Eppendorf, 20246- Hamburg, Germany; and
^* Kreiskrankenhaus Rendsburg, Gynäkologische Abteilung, 24768 Rendsburg, Germany

²Correspondence: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology, Friedrich-Alexander-University Erlangen-Nuremberg, Fahrstr. 17, D-91054 Erlangen, Germany. E-mail: thomas.eschenhagen{at}pharmakologie.uni-erlangen.de

Sensitization of adenylyl cyclase (AC) by increased expression of large isoforms of the stimulatory G-protein G_s has been suggested as a mechanism that governs uterine quiescence during pregnancy. We quantified several components of the AC pathway in pregnant (P, n=21) and nonpregnant human myometria (NP, n=10). AC activity was ~sevenfold higher in P than in NP under basal and stimulated conditions (MnCl₂/GTP/GTP + isoproterenol). In addition, relative stimulation (% of basal) by 5'-guanosine-ß-iminotriphosphate and forskolin was twofold higher in P. ß-Adrenoceptor density was low and unaltered in P. G_s mRNA splice variants did not differ in P. Using antisera against different epitopes of G_s (carboxyl-/more amino-terminal), we found unchanged expression of G_s short and long (45, 47 kDa) in P. Two additional proteins in P (51, 59 kDa) were detectable only by the carboxyl-terminal antiserum and lacked GTP binding properties. The 59 kDa protein could be identified as a recently discovered cytoskeletal protein, smoothelin, which was 10-fold increased in P. These data indicate that the apparent up-regulation of large G_s species in P is mimicked by elevated smoothelin. Therefore, the increase in AC cannot be attributed to changes in G_s- or ß-adrenoreceptors. Epitope sharing between G_s and smoothelin should be considered in experiments on smooth muscle tissues.—Gsell, S., Eschenhagen, T., Kaspareit, G., Nose, M., Scholz, H., Behrens, O., Wieland, T. Apparent up-regulation of stimulatory G-protein subunits in the pregnant human myometrium is mimicked by elevated smoothelin expression.

Key Words: epitope sharing • smooth muscle • G_s mRNA expression • adenylyl cyclase

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