Table of Contents

June 2002; 2 (3)

Speaking of Pharmacology




  • A recent publication by Gaietta et al. describes the real-time trafficking of connexin, and through the use of different fluors, researchers can discriminate between “older” and newly synthesized connexins. Goodenough and Postma discuss how the technique permits the visualization of dynamic building and degradation that occurs in subcellular compartments, and how the method can be used to analyze protein fates in real time.

  • Petäjä-Repo et al. have published a recent article describing how ligands for delta opioid receptors can facilitate the maturation of delta opioid receptors at the endoplasmic reticulum (ER) and promote the surface expression of these receptors. Indeed, even antagonists of the receptor can promote receptor maturation. Bartlett and Whistler discuss the findings within the article and how chaperones can rescue immature receptors from proteasome-dependent degradation. Pharmacological interventions can be designed that target immature ER-bound receptors, and subsequently, facilitate their maturation or degradation to ameliorate pathological conditions associated with abnormal surface expression of receptors.

  • Sunnarborg et al. have published how tumor necrosis factor-α converting enzyme (TACE) can control the availability of transforming growth factor-α—a natural ligand for epidermal growth factor receptors (EGFRs)—for EGFRs located at the cell surface. Dempsey, Garton, and Raines examine the ramifications of TACE-dependent proteolytic cleavage of membrane-bound ligands on paracrine, juxtacrine, and autocrine signaling.

  • Two publications by Mecklenbräuker et al. and Miyamoto et al. describe an essential role for protein kinase Cδ (PKCδ) in the development of immune tolerance, and suggest that PKCδ also participates in mechanisms that prevent autoimmunity. Su, Guo, and Rawlings discuss these observations within the larger context of determining specific functions for individual isoforms of PKC in B and T lymphocytes, and the careful control these proteins exert in maintaining proper lymphocyte activation and tolerance.


  • Drugs of abuse affect the mechanisms by which the brain processes learning and memory events. Chronically abused substances wreak havoc with the ability of neurons to undergo normal long-term potentiation (LTP) and long-term depression (LTD), resulting in maladaptive learning and in the reinforcement of craving and drug-seeking behavior. Changes in neuronal plasticity are now being successfully mapped to account for drug-related behavioral responses.

  • Like a distant thunderclap growing louder and furiously rolling closer to an observer, the research field that encompasses RNA silencing (RNA interference or RNAi) has recently exploded with examples of RNAi-mediated regulation in cultured mammalian cells. Now, RNAi is being exploited to validate protein targets for pharmaceutical intervention, and might prove useful in correcting genetic abnormalities or metabolically based diseases through gene therapy.

  • Great advances have been made recently in elucidating the structures of adenylyl cyclases (ACs), and in discovering many of the proteins and small molecules that affect their catalytic activity. Further discovery and refinement of existing observations will lead to better, more intelligent design of pharmacological therapeutics that can correct abnormal AC activity in disease states.

Beyond the Bench

Net Results