Cvek K, Ridderstråle Y, Gerstberger R
Department of Animal Physiology, Swedish University of Agricultural Sciences, Uppsala.
Endocrinology. 1998 May;139(5):2615-21. doi: 10.1210/endo.139.5.5996.
The present study was undertaken: 1) to localize and characterize atrial natriuretic peptide (ANP) receptors in the rat mammary gland; and 2) to elucidate ANP-induced cellular formation of cyclic GMP (cGMP) and alterations in alveolar morphology during both early and late lactation. Receptor autoradiography, employing rat-specific [125I]ANP as radioligand, demonstrated binding sites in the secretory tissue and larger blood vessels of the mammary gland. Binding of [125I]rANP to membrane fractions was completely displaced by unlabeled ANP and brain natriuretic peptide. C-type natriuretic peptide and cANP(4-23) revealed limited competition with radiolabeled ANP only during early lactation, indicating a more heterogeneous receptor population at that time. Systemically administered ANP induced cGMP formation in the alveolar epithelium, as shown with immunohistochemistry, and increased mammary tissue cGMP concentrations in vivo throughout the lactation period. Image analysis revealed enlargement of alveolar (but not epithelial) cell area after ANP stimulation in late lactation, suggesting altered alveolar filling or myoepithelial cell relaxation. These results indicate that ANP induces biological effects in the rat mammary gland through specific ANP-A receptor interaction with subsequent intracellular cGMP formation. ANP may therefore play a regulatory role in the control of mammary gland blood supply and secretory function.
1）定位并表征大鼠乳腺中的心房利钠肽（ANP）受体；2）阐明在泌乳早期和晚期ANP诱导的细胞内环磷酸鸟苷（cGMP）的形成以及肺泡形态的改变。采用大鼠特异性[125I]ANP作为放射性配体的受体放射自显影显示，在乳腺的分泌组织和较大血管中有结合位点。[125I]rANP与膜组分的结合被未标记的ANP和脑利钠肽完全取代。C型利钠肽和cANP(4-23)仅在泌乳早期显示出与放射性标记的ANP的有限竞争，表明此时受体群体更为异质。全身给予ANP可诱导肺泡上皮细胞中cGMP的形成，免疫组织化学显示，在整个泌乳期体内乳腺组织中cGMP浓度升高。图像分析显示，在泌乳晚期ANP刺激后肺泡（而非上皮）细胞面积增大，提示肺泡充盈改变或肌上皮细胞松弛。这些结果表明，ANP通过与特定的ANP-A受体相互作用并随后形成细胞内cGMP在大鼠乳腺中诱导生物学效应。因此，ANP可能在乳腺血液供应和分泌功能的控制中发挥调节作用。
