661W cells demonstrate cellular and biochemical characteristics exhibited by cone photoreceptor cells. These cells also resemble neuronal cells with their spindlelike processes and should serve as a useful alternative in vitro model for the study of cone photoreceptor cell biology and associated diseases.

The cysteinyl leukotrienes (CysLTs) mimic many of the features of asthma and are implicated in its pathophysiology. Little, however, is known about the effects of the CysLTs on airways remodeling. In this study the effects of leukotriene D4 (LTD4) on human airway smooth muscle (HASM) cell proliferation and expression of extracellular matrix proteins were investigated. LTD4 (0.1-10 microM) alone had no effect on DNA synthesis in HASM. LTD4, however, markedly augmented proliferation induced by the mitogen, epidermal growth factor (EGF, 1 ng/ml). The potentiating effect of LTD4 (1 microM) on EGF-induced DNA synthesis was abolished by pranlukast (1 microM) or pobilukast (30 microM), but unaffected by zafirlukast (1 microM). In contrast, pranlukast (pKB = 6.9), pobilukast (pKB = 7.0), and zafirlukast (pKB = 6.5) had equivalent potencies for inhibition of LTD4-induced contraction in human bronchus. LTD4 (0.1 or 10 microM) did not increase the total messenger RNA expression of the extracellular matrix proteins (pro-alpha[I] type I or alpha1[IV] type IV collagen), elastin, biglycan, decorin, and fibronectin, and did not influence tumor growth factor-beta (10 ng/ml)-induced effects on the expression of these proteins in HASM cells. These data indicate that LTD4 augments growth factor-induced HASM proliferation but does not alter the expression of various extracellular matrix components. The observed differences in sensitivity to the antagonists suggests that the former phenomenon may be mediated by a CysLT receptor distinct from that which mediates LTD4-induced HASM contraction. Collectively, these results provide preliminary evidence that CysLTs may play a role in airways remodeling in asthma.

Genetic strategies for perturbing activity of selected neurons hold great promise for understanding circuitry and behavior. Several such strategies exist, but there has been no direct demonstration of reversible inactivation of mammalian neurons in vivo. We previously reported quickly reversible inactivation of neurons in vitro using expression of the Drosophila allatostatin receptor (AlstR). Here, adeno-associated viral vectors are used to express AlstR in vivo in cortical and thalamic neurons of rats, ferrets, and monkeys. Application of the receptor's ligand, allatostatin (AL), leads to a dramatic reduction in neural activity, including responses of visual neurons to optimized visual stimuli. Additionally, AL eliminates activity in spinal cords of transgenic mice conditionally expressing AlstR. This reduction occurs selectively in AlstR-expressing neurons. Inactivation can be reversed within minutes upon washout of the ligand and is repeatable, demonstrating that the AlstR/AL system is effective for selective, quick, and reversible silencing of mammalian neurons in vivo.