saporin

Taylor AM, Osikowicz M, Ribeiro-da-Silva A (2012) Consequences of the ablation of nonpeptidergic afferents in an animal model of trigeminal neuropathic pain. Pain 153(6):1311-1319. doi: 10.1016/j.pain.2012.03.023

Summary: The authors used IB4-SAP (Cat. #IT-10; 3.2 μg injected into the mental nerve) to eliminate C-fibers in the lower lip of rats to see if this was enough to induce the sprouting of autonomic fibers. Saporin alone (Cat. #PR-01) was used as a control. Only parasympathetic fibers sprouted in these animals, but after nerve ligation surgery both sympathetic and parasympathetic fibers sprouted.

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Ye Y, Dang D, Viet CT, Dolan JC, Schmidt BL (2012) Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity. J Pain 13(6):524-531. doi: 10.1016/j.jpain.2012.01.006

Summary: DOR (δ opioid receptor) agonists produce minimal side effects and do not lead to tolerance, making them potential alternatives to the widely used μ opioid receptor agonists. Utilizing the fact that DOR’s are expressed by IB4-positive neurons, the authors injected the subarachnoid space between the L4 and L5 vertebrae of rats with 2.4 μg of IB4-SAP (Cat. #IT-10). 3 μg of saporin (Cat. #PR-01) was used as a control. The results indicate that pharmacological agents targeting IB4-positive neurons may have use in cancer pain treatment.

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Han N, Zu JY, Chai J (2012) Spinal bombesin-recognized neurones mediate more nonhistaminergic than histaminergic sensation of itch in mice. Clin Exp Dermatol 37(3):290-295. doi: 10.1111/j.1365-2230.2011.04314.x

Summary: The authors administered 400 ng of Bombesin-SAP (Cat. #IT-40) to the lumbar spinal subarachnoid space of rats and evaluated the distribution of Fos-positive cells in the dorsal horn after stimulation. Saporin (Cat. #PR-01) was used as a control. The results demonstrate that the neurons eliminated by Bombesin-SAP are critical to both acute and chronic itch pathways, although they have more effect on nonhistaminergic sensation.

Related Products: Bombesin-SAP (Cat. #IT-40), Saporin (Cat. #PR-01)

Selbo PK, Weyergang A, Eng MS, Bostad M, Maelandsmo GM, Hogset A, Berg K (2012) Strongly amphiphilic photosensitizers are not substrates of the cancer stem cell marker ABCG2 and provides specific and efficient light-triggered drug delivery of an EGFR-targeted cytotoxic drug. J Control Release 159(2):197-203. doi: 10.1016/j.jconrel.2012.02.003

Summary: Many anti-cancer drugs are substrates of the ATP-binding cassette transporter ABCG2. Unfortunately ABCG2 is also thought to play an important role in multi-drug resistance and the protection of cancer stem cells against chemotherapeutics and photodynamic therapy. This paper examined whether photosensitizers used in photochemical internalization (PCI) are substrates for ABCG2. Streptavidin-ZAP (Cat. #IT-27) was combined with biotinylated EGF and applied to cells in culture; saporin (Cat. #PR-01) was used as a control. The data show that PCI with the EGF-saporin toxin did not utilize ABCG2 to enter cells.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01)

Minami SS, Sun B, Popat K, Kauppinen T, Pleiss M, Zhou Y, Ward ME, Floreanig P, Mucke L, Desai T, Gan L ( 2012 ) Selective targeting of microglia by quantum dots. J Neuroinflammation 9(1):22 . doi: 10.1186/1742-2094-9-22

Related Products: MonoBiotin-ZAP (Cat. #BT-ZAP)

Choi JI, Koehrn FJ, Sorkin LS (2012) Carrageenan induced phosphorylation of Akt is dependent on neurokinin-1 expressing neurons in the superficial dorsal horn. Mol Pain 8(1):4. doi: 10.1186/1744-8069-8-4 PMID: 22243518

Summary: In this work the authors administered 100 ng SSP-SAP (Cat. #IT-11) into the intrathecal space of rats (saporin, Cat. #PR-01, was used as a control). Lesioned animals displayed decreased carrageenan-induced mechanical allodynia, and carrageenan-induced phosphorylation of Akt was blocked throughout the spinal cord gray matter. Anti-NK-1 (Cat. #AB-N33AP) was used for immunohistochemistry.

Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01), NK-1 Receptor Rabbit Polyclonal, affinity-purified (Cat. #AB-N33AP)

Staudt MD, Truitt WA, McKenna KE, de Oliveira CV, Lehman MN, Coolen LM (2012) A pivotal role of lumbar spinothalamic cells in the regulation of ejaculation via intraspinal connections. J Sex Med 9(9):2256-2265. doi: 10.1111/j.1743-6109.2011.02574.x

Summary: The authors examined the hypothesis that specific lumbar spinothalamic (LSt) cells control ejaculation through intraspinal connections. Rats received six bilateral injections of SSP-SAP (Cat. #IT-11) into the spinal cord, 48 ng in total. Saporin (Cat. #PR-01) was used as a control. It was found that while erectile function and emission were not affected, the usual rhythmic contractions of the bulbocaveronosus muscle during ejaculation were prevented.

Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01)

Read the featured article in Targeting Trends.

Talman WT, Nitschke Dragon D, Jones S, Moore SA, Lin L-H (2011) Cardiovascular dysfunction and cardiac injury result from selective glial damage in the nucleus tractus solitarii. Neuroscience 2011 Abstracts 664.14. Society for Neuroscience, Washington, DC.

Summary: In man, extensive CNS dysfunction as may occur after subarachnoid hemorrhage may lead to cardiac damage and cardiac arrhythmias. We have shown that highly selective and restricted lesions of the nucleus tractus solitarii (NTS) may lead to similar cardiac and cardiovascular compromise. For example, using conjugates including the cytotoxin saporin (SAP) to selectively damage NTS neurons that express NK1 receptors or those that express tyrosine hydroxylase (TH) leads to cardiac dysfunction and associated lability of arterial pressure. In continuing efforts to better characterize cellular changes produced by introducing into the NTS conjugates containing SAP, we have studied the effect of anti-dopamine-beta-hydroxylase (anti-DBH)-SAP, stabilized substance P (SSP)-SAP, SAP (unconjugated), blank-SAP (non-targeted peptide conjugate), IgG-SAP (non-targeted immunoglobulin conjugate), and 6-hydoxydopamine (6-OHDA) as a control without SAP injected into NTS. We assessed effects of the injected agents both on cellular markers [NMDAR1 (NMDA receptor subunit 1), GluR2 (AMPA receptor subunit 2), gamma-aminobutyric acid (GABA) receptor type a and b, neuronal nitirc oxide synthase (nNOS), TH, vesicular glutamate transporters (VGluTs), choline acetyl transferase (ChAT), glial fibrillary acidic protein (GFAP), connexin 43 (Cx43), DBH and protein gene product 9.5 (PGP 9.5)] and on cardiovascular and cardiac function. We have found that each compound containing SAP (including blank-SAP, IgG-SAP, unconjugated SAP) led to loss of GFAP and Cx43 immunofluorescent labeling in the NTS as well as lability of arterial pressure, cardiac arrhythmias, and cardiac myocytolysis. Those outcomes occurred despite neuronal specificity for each of the SAP conjugates. For example, anti-DBH-SAP led to a decrease in TH and DBH staining as well as a profound loss in GFAP and Cx43. In contrast, SSP-SAP led to loss of NK1 as well as GFAP, Cx43, and glutamate receptor markers but did not lead to loss of DBH or GABA. SSP-SAP also caused a loss in PGP9.5 which was not observed in all other agents. SAP and blank-SAP, on the other hand, led to loss of GFAP and Cx43 while 6-OHDA led to loss of TH and DBH, increased GFAP and decreased Cx-43. We are still investigating the effects of 6-OHDA on lability of arterial pressure and cardiac events but preliminary data suggest that, in doses used, it led to loss of TH and DBH but did not lead to either lability or cardiac events that were seen with each of the conjugates containing an SAP moiety. This study suggests that glial dysfunction may alone interefere with cardiovascular control through the NTS and may lead to cardiac damage and cardiovascular dysfunction.

Related Products: Anti-DBH-SAP (Cat. #IT-03), SSP-SAP (Cat. #IT-11), Mouse IgG-SAP (Cat. #IT-18), Blank-SAP (Cat. #IT-21), Saporin (Cat. #PR-01)

Ritter S, Li A-J, Wang Q, Dinh TT (2011) Basal metabolic substrate utilization is altered by lesion of hindbrain catecholamine neurons that innervate the medial hypothalamus and substrate selection during glucoprivation is impaired. Neuroscience 2011 Abstracts 88.05. Society for Neuroscience, Washington, DC.

Summary: Central injection of the targeted immunotoxin, anti-dopamine beta hydroxylase (DBH)-saporin (DSAP), retrogradely and selectively lesions norepinephrine (NE) and epinephrine (E) neurons with projections to the injection site. Previous work has shown that DSAP injections targeting the hypothalamic paraventricular nucleus eliminate key counterregulatory responses to acute glucose deficit, including feeding and corticosterone secretion. To examine the role of these NE an E neurons in metabolic control under basal conditions, we injected rats in the PVH with DSAP or control unconjugated saporin (SAP) and analyzed their metabolic profiles using metabolic chambers (Columbus Instruments). Rats were maintained on a standard pelleted rodent diet. We found that the respiratory exchange ratio (RER) was consistently elevated in DSAP rats across the entire circadian cycle under basal conditions, compared to the RER of SAP controls, indicating increased dependence on carbohydrate utilization. Metabolic rate and activity did not differ between groups. This result suggests a chronic enhancement of glucose mobilization or an impairment of the ability to mobilize fatty acids in the DSAP rats. We also found that when challenged by 2-deoxy-D-glucose induced glucoprivation, SAP controls exhibited a rapid decrease in RER, indicating a switch to fat metabolism, whereas DSAP rats did not exhibit this response. Together these results favor the possibility that a central mechanism for fat mobilization is impaired in DSAP rats and that this impairment is reflected under both basal and glucoprivic conditions. The previously reported observation that PVH DSAP-injected rats exhibit a slowly-developing obesity also supports this possibility. Additional findings suggest that this impairment may be due to the loss of NE/E control of corticosterone secretion in the DSAP rats.

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

I’anson H, Jethwa PH, Warner A, Ebling FJ (2011) Histaminergic regulation of seasonal metabolic rhythms in Siberian hamsters. Physiol Behav 103(3-4):268-278. doi: 10.1016/j.physbeh.2011.02.035

Summary: The role of central histaminergic mechanisms on seasonal catabolic state was investigated in hamsters. Siberian hamsters received bilateral 3.8-ng injections of orexin-SAP (Cat. #IT-20) into the tuberomammillary posterior hypothalamic region. Saporin (Cat. #PR-01) was used as a control. During long days, lesioned animals displayed higher locomotor activity, greater oxygen intake, and no net weight gain. During shorter days (hibernation) with less activity, lesioned animals did not lose weight. The data indicate that histaminergic neurons are involved in body weight regulation.

Related Products: Orexin-B-SAP (Cat. #IT-20), Saporin (Cat. #PR-01)