FUNCTIONAL RECEPTORS FOR ATRIAL-NATRIURETIC-PEPTIDE IN THE RAT MAMMARY-GLAND DURING LACTATION

The present study was undertaken: 1) to localize and characterize atri al 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 lactati on. Receptor autoradiography, employing rat-specific [(125)1] ANP as r adioligand, demonstrated binding sites in the secretory tissue and lar ger blood vessels of the mammary gland. Binding of [I-125]rANP to memb rane fractions was completely displaced by unlabeled ANP and brain nat riuretic 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. Sys temically administered ANP induced cGMP formation in the alveolar epit helium, as shown with immunohistochemistry, and increased mammary tiss ue cGMP concentrations in vivo throughout the lactation period. Image analysis revealed enlargement of alveolar (but not epithelial) cell ar ea after ANP stimulation in late lactation, suggesting altered alveola r filling or myoepithelial cell relaxation. These results indicate tha t ANP induces biological effects in the rat mammary gland through spec ific ANP-A receptor interaction with subsequent intracellular cGMP for mation. ANP may therefore play a regulatory role in the control of mam mary gland blood supply and secretory function.