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We have performed a high-capacity, semiquantitative, reverse transcriptase-polymerase chain reaction screen for expression of fibroblast growth factor (FGF) and transforming growth factor beta (TGFbeta) family genes as well as their cognate receptors. By using cDNA prepared from embryonic day 12 to postnatal day 0 embryonic mouse pancreas, we have identified several factors potentially involved in the development of the endocrine pancreas. We find high-level early expression of TGFbeta-1 and -2, and constitutive expression of TGFbeta-3 and their receptors. Of the Inhibin/Activin members, we found exclusively Inhibin-alpha and Activin-betaB to be expressed, and the BMP family was represented by BMP4, BMP5, and BMP7. The predominant forms of the BMP and Activin type II receptors were ActR-IIB and BMPR-II and of the type I receptors, BMPR-1A and -1B were the highest expressed. FGF1, FGF7, FGF9, FGF10, FGF11, and FGF18 were also expressed in the pancreas at varying time points and levels, as well as FGF receptor forms FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, and FGFR4. To gain insight into the biological function, we misexpressed members of these families in the pancreas by using the early pancreas promoter Pdx1. Misexpression of FGF4 results in disruption of the pancreas morphology with epithelial structures interspersed in stroma tissue. The endocrine compartment was reduced to scattered single cells, and the exocrine consisted of unbranched ductal epithelia with acinar structures budding off. In contrast, misexpression of BMP-6 resulted in complete agenesis of the pancreas and reduced the size of the stomach and spleen dramatically and caused fusion of the liver and duodenum.

Sulfidopeptide leukotrienes (LTs) include LTC4, LTD4, and LTE4. They contract airway smooth muscle and reduce heart contractility in mammals. In this study, LTC4, LTD4, and LTE4 were compared for their effects on bullfrog heart and lung contractility in vitro. LTC4, LTD4, and LTE4 all stimulated lung contraction and increased heart contractility, but LTC4 was more potent than the other two leukotrienes. LY 171883, a mammalian LTD4 receptor antagonist, failed to block the heart and lung responses to LTC4 but did blunt the responses to LTD4 and LTE4. Metabolism studies carried out with 3H-LTC4 demonstrated conversion to LTD4 and small amounts of LTE4 by heart, but not by lung. Thus, bullfrogs respond to leukotrienes in ways which may be similar to (increase in lung contractility) or different from (increase in heart contractility) mammals. Leukotriene receptors appear to be highly conserved, despite the fact that tissue responsiveness to leukotrienes has changed over evolutionary time.