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Functional Receptors for Atrial Natriuretic Peptide in the Rat Mammary Gland during Lactation¹

Department of Animal Physiology (K.C., Y.R.), Swedish University of Agricultural Sciences, S-75007 Uppsala, Sweden; and Max-Planck-Institute for Physiological and Clinical Research (R.G.), W. G. Kerckhoff Institute, D-61231 Bad Nauheim, Germany

Address all correspondence and requests for reprints to: Dr. Katarina Cvek, Department of Animal Physiology, Swedish University of Agricultural Sciences, Box 7045, S-750 07 Uppsala, Sweden. E-mail: katarina.cvek{at}djfys.slu.se

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 heterogenous 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.