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

Sensitization of adenylyl cyclase (AC) by increased expression of large isoforms of the stimulatory G‐protein Go 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 ~sev‐enfold higher in P than in NP under basal and stimulated conditions (MnCl 2 /GTP/GTP + isopro‐terenol). In addition, relative stimulation (% of basal) by 5’‐guanosine‐β7‐iminotriphosphate and forskolin was twofold higher in P. β‐Adrenoceptor density was low and unaltered in P. Go s mRNA splice variants did not differ in P. Using antisera against different epitopes of Go s (carboxyl‐/more amino‐terminal), we found unchanged expression of Go 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 Go s species in P is mimicked by elevated smoothelin. Therefore, the increase in AC cannot be attributed to changes in Go s ‐or β‐adrenoreceptors. Epitope sharing between Go 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 α subunits in the pregnant human myometrium is mimicked by elevated smoothelin expression. FASEB J. 14, 17–26(2000)