Table of Contents

March 2003; 3 (2)

Speaking of Pharmacology




  • Foxglove and its constituents therapeutic agent digitalis have been used for centuries for the treatment of heart failure. All digitalis-like cardiotonic steroids enhance heart contraction through a mechanism involving the inhibition of the Na+,K+– ATPase. Recentlt, Rathore and colleagues reported that sex-based differences may exist in the efficacy of digoxin for the treatment of heart failure. The authors of the study found that female patients exhibited increased risk of death associated with digoxin therapy, whereas male patients appeared to have no increased risk of death related to digoxin therapy. Blaustein and colleagues delve into the report and discuss possible explanations for these findings, suggest alternative ones, and advocate for enrolling greater numbers of women in clinical studies.

  • A second form of tryptophan hydroxylase (TPH) is expressed in the brain by the gene Tph2. The presence of the gene was discovered when Tph 1–/–mice were found to express normal amounts of serotonin in brain, but not in the periphery. Additionally, Tph1–/– mice showed no observed behavioral differences from wild-type littermates. Veenstra-Vanderweele and Cook discuss the ramifications of these findings and what they might mean for designing drugs that target the expression and activity of TPH in differing tissues.

  • B lymphocytes and T lymphocytes utilize several proteins with common functions to transduce signals from their respective receptors. However, at the hierarchial signalling level of SLP-76 [Src homology 2(SH2) domain-containing leukocyte protein of 76-kDa] and LAT (linker for activation of T cells) in T cells, the only corresponding protein in B cells was known to be BLNK (B cell linker protein). It was thought that perhaps BLNK performed the cognate roles of SLP-76 and LAT in B cells; however, mounting evidence to the contrary revealed that this hypothesis was not robust. Two laboratories have recently described the characterization of a protein expressed in B cells and myeloid cells, alternatively termed NTAL (non-T cell activation linker) or LAB (linker for activation of B cells). NTAL/LAB and LAT may have arisen from a primordial gene-duplicating event, but genes that code for the two proteins do not share a very high degree of sequence identity. Wange discusses the results of the two reports, the evidence for functional homology between LAT and NTAL/LAB, and the possibility that the differences between them might lead to specific clinical therapeutics to manipulate immnue cell responses.


  • That smooth muscles dilate and contract rhythmically has been known for a long time and the phenomenon has been studied for nearly as long. However, the causes and effects of smooth muscle oscillation (termed vasomotion) are far from clear. It is thought that vasomotion aids the delivery of oxygen to tissues surrounding capillary beds. On the other hand, unregulated vasomotion might participate in the development and maintenance of pathophysiological states. Nilsson and Aalkjær review what is known about vasomotion and its consequences.

  • As human longevity increases, the likelihood of the onset of diseases of the brain (and other organs) also increases. Clinical therapeutics offer useful long-term treatments, if not cures, if drugs can be delivered appropriately and effectively. Unfortunately, research in drug transport to the brain has not advanced very far. Through better characterization of the transport systems utilized within the blood–brain barrier, a greater understanding of how to exploit these systems will lead to effective treatments for brain disorders. Pardridge reviews the functions of the various known transport systems in the brain and discusses how the development of BBB drug-targeting programs in pharmaceutical and academic settings may lead to more efficacious treatments.

Beyond the Bench


Net Results