Several aspects of regulation of receptor signal transduction have been studied using a neurohybrid NCB-20 cell line. Activators of voltage sensitive sodium channels such as batrachotoxin and a sodium ionophore monensin induced a Ca(2+)-dependent increase in the production of inositol phosphates including IP1, IP2, and IP3. Veratridine was found to drastically inhibit the phosphoinositide (PI) turnover induced by carbachol. Adenosine selectively inhibited the PI response to histamine mediated by H1 receptors. This inhibition was reversible and insensitive to pertussis toxin. our data indicate that this modulation represents a cross-talk, probably involving the two second messengers, inositol phos- phate and cyclic AMP. We also have compared mechanisms of induction of delta-opioid receptors by long-term treatment with sodium butyrate and naltrexone. While the butyrate's effect involves new protein synthesis and the transport of newly synthesized receptors to the plasma membrane via receptor-G protein complexes in light membrane vesicles, the naltrexone-induced receptor induction in NG108-15 cells appears to mainly involve a decreased degradation due to a drastic reduction in the lysosomal enzyme activity, indicating that distinct mechanisms of delta-opioid receptor up-regulation are involved.
