2007 Targeting Trends Review

Rahman W, Sikander S, Suzuki R, Hunt SP, Dickenson AH (2007) Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors. Neurosci Lett 419:278-283. doi: 10.1016/j.neulet.2007.04.039

Summary: It has been shown that elimination of lamina 1 NK1 receptor-expressing neurons affects pain behaviors. The authors investigated whether eliminating these neurons would alter GABAergic spinal inhibitory systems. Rats received 10-µl injections of 10-µM SP-SAP (Cat. #IT-07) into the L4-5 regions. Data generated by electrical and mechanical stimuli suggest that although GABAergic transmission is dependent on NK1 receptor-expressing neurons, loss of these cells results in a decrease in spinal cord excitability.

Related Products: SP-SAP (Cat. #IT-07)

Gibbs RB (2007) Estradiol enhances DMP acquisition via a mechanism not mediated by turning strategy but which requires intact basal forebrain cholinergic projections. Horm Behav 52:352-359. doi: 10.1016/j.yhbeh.2007.05.011

Summary: Estradiol appears to enhance cholinergic projections to the hippocampus and frontal cortex as shown by tests of response patterns and strategy in rats. The author tested whether this affect was involved with turning strategy, defined as which arm was chosen first in a T-maze. 0.22 µg injections of 192-IgG-SAP (Cat. #IT-01) were made into the medial septum of rats. Lesioned animals utilized a persistent turning strategy; they always chose the same arm of the maze first, even after the administration of estradiol. These data suggest that although the effects of estradiol are not linked to turning strategy, estradiol does interact with the cholinergic system.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Wiley RG, Kline IV RH, Vierck Jr CJ (2007) Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar(9),Met(O(2))(11)]-substance P-saporin: Behavioral and anatomical analyses. Neuroscience 146:1333-1345. doi: 10.1016/j.neuroscience.2007.01.066

Summary: While lumbar injections of SP-SAP (Cat. #IT-07) produce specific lesions, use of this targeted conjugate in the forebrain has been problematic. The authors investigated the use of SSP-SAP (Cat. #IT-11), a conjugate of saporin with a stable analog of substance P. The greater stability of SSP-SAP resulted in increased potency as well as better specificity. SSP-SAP is shown to be a highly effective reagent for the removal of NK1 receptor-expressing neurons in the brain and spinal cord.

Related Products: SP-SAP (Cat. #IT-07), SSP-SAP (Cat. #IT-11)

Hanganu IL, Staiger JF, Ben-Ari Y, Khazipov R (2007) Cholinergic modulation of spindle bursts in the neonatal rat visual cortex in vivo. J Neurosci 27:5694-5705. doi: 10.1523/JNEUROSCI.5233-06.2007

Summary: The authors investigated the relationship between cholinergic drive and spindle burst oscillation driven by retinal waves. 0.5 µl of 0.2-µg/µl 192-IgG-SAP (Cat. #IT-01) was injected into both ventricles of rat pups. The lesioned animals displayed markedly decreased oscillatory activity. Since this activity may be used as a functional template for cortical networks and architecture, the results suggest a link between cholinergic activity and cortical development.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Schiltz JC, Sawchenko PE (2007) Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults. J Comp Neurol 502:455-467. doi: 10.1002/cne.21329

Summary: Interleukin-1 (IL-1) is one of the cytokines that mediates interactions between the immune system and the central nervous system. 380-ng injections of anti-DBH-SAP (Cat. #IT-03) were made into the paraventricular nucleus (PVH) of rats. Saporin (Cat. #PR-01) and mouse IgG-SAP (Cat. #IT-18) were used as controls. Lesioned animals demonstrated reduced responses to administration of IL-1, but restraint stress responses were left intact. The data suggest that ascending catecholaminergic projections mediate PVH response to IL-1.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01), Mouse IgG-SAP (Cat. #IT-18)

Bak SP, Walters JJ, Takeya M, Conejo-Garcia JR, Berwin BL (2007) Scavenger receptor-A-targeted leukocyte depletion inhibits peritoneal ovarian tumor progression. Cancer Res 67:4783-4789. doi: 10.1158/0008-5472.CAN-06-4410

Summary: Vascular leukocytes (VLC) are immunosuppressive cells that facilitate tumor progression in ovarian cancer. One potential tumor therapy is to eliminate these cells. The authors determined that scavenger receptor-A is specifically expressed on VLCs. Mice were injected with tumor cells, as well as an anti-scavenger receptor-A antibody combined with Rat-ZAP (Cat. #IT-26). This was followed by additional treatment with the antibody-Rat-ZAP complex. Treatment with the immunotoxin eliminated VLCs, inhibited peritoneal tumor burden, and reduced ascites accumulation.

Related Products: Rat-ZAP (Cat. #IT-26)

Elson-Schwab L, Garner OB, Schuksz M, Esko JD, Tor Y (2007) Guanidinylated-Neomycin delivers large, bioactive cargo into cells through a heparan sulfate dependent pathway. J Biol Chem 282(18):13585-13591. doi: 10.1074/jbc.M700463200

Summary: The uptake of high molecular weight drugs into cells is a stumbling block for some potential therapeutics. Using a neomycin derivative in which guanidinium groups have replaced the ammonium groups, the authors show heparan sulfate-dependent uptake of large molecules. The guanidine-neomycin was biotinylated, and incubated with streptavidin-ZAP (Cat #IT-27). This complex was effective in killing CHO cells in vitro, but was no more effective than streptavidin-ZAP alone on cells lacking heparan sulfate expression, demonstrating specificity.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Myhrer T, Enger S, Aas P (2007) Anticonvulsant effects of damage to structures involved in seizure induction in rats exposed to soman. Neurotoxicology 28(4):819-828. doi: 10.1016/j.neuro.2007.03.010

Summary: Soman is a nerve agent that irreversibly inhibits acetylcholinesterase, resulting in respiratory dysfunction, seizures, convulsions, coma, and death. In this work the authors investigated whether elimination of cholinergic pathways in the medial septum (MS) or diagonal band nucleus (DBN) would affect the onset of convulsions. 0.3 µl of 0.5-µg/µl 192-IgG-SAP (Cat. #IT-01) was infused into the MS and/or DBN. Lesioned animals still experienced convulsions, suggesting that cholinergic MS systems are not the only ones involved.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Gibbs RB, Johnson DA (2007) Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy. Neurobiol Learn Mem 88:19-32. doi: 10.1016/j.nlm.2007.03.007

Summary: It has been well established that the cholinergic system of the basal forebrain plays a critical role in many cognitive processes. This work utilized injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum, the nucleus basalis magnocellularis, or both to examine the lesioning effect on two cognitive tasks in rats. The data indicate that cholinergic lesions of the basal forebrain produce learning deficits that are task specific, and that learning is affected without corresponding deficits in memory.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Hess PR, Barnes C, Woolard MD, Johnson MD, Cullen JM, Collins EJ, Frelinger JA (2007) Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin. Blood 109:3300-3307. doi: 10.1182/blood-2006-06-028001

Objective: To discover if pathogenic T cells could be selectively deleted.

Summary: A single injection of the SAP-coupled tetramer eliminated more than 75% of cognate, but not control, T cells. This work demonstrates the therapeutic potential of cytotoxic tetramers to selectively eradicate pathogenic clonotypes while leaving overall T-cell immunity intact.

Usage: Streptavidin-SAP-coupled biotinylated tetramers were administered at low (22.2 pM) or high (66.6 pM) dose. Following the addition of Saporin Goat Polyclonal, affinity-purified FITC-labeled, T cells were subsequently incubated at either 37°C or 4°C, which permitted or prohibited endocytosis, respectively.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

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