Apparent up-regulation of stimulatory G-protein alpha subunits in the pregnant human myometrium is mimicked by elevated smoothelin expression.
Sensitization of adenylyl cyclase (AC) by increased expression of large isoforms of the stimulatory G-protein Galpha(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 approximately sevenfold higher in P than in NP under basal and stimulated conditions (MnCl(2)/GTP/GTP + isoproterenol). In addition, relative stimulation (% of basal) by 5'-guanosine-betagamma-iminotriphosphate and forskolin was twofold higher in P. beta-Adrenoceptor density was low and unaltered in P. Galpha(s) mRNA splice variants did not differ in P. Using antisera against different epitopes of Galpha(s) (carboxyl-/more amino-terminal), we found unchanged expression of Galpha(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 Galpha(s) species in P is mimicked by elevated smoothelin. Therefore, the increase in AC cannot be attributed to changes in Galpha(s)- or beta-adrenoreceptors. Epitope sharing between Galpha(s) and smoothelin should be considered in experiments on smooth muscle tissues.[1]References
- Apparent up-regulation of stimulatory G-protein alpha subunits in the pregnant human myometrium is mimicked by elevated smoothelin expression. Gsell, S., Eschenhagen, T., Kaspareit, G., Nose, M., Scholz, H., Behrens, O., Wieland, T. FASEB J. (2000) [Pubmed]
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