Chance WT, Dayal R, Friend LA, Sheriff S (2006) Possible role of CRF peptides in burn-induced hypermetabolism. Life Sci 78(7):694-703. doi: 10.1016/j.lfs.2005.05.083

Summary: Burn trauma has been associated with hypermetabolism and anorexia. Corticotropin releasing factor (CRF) elevates metabolic rate and elicits anorexia, while neuropeptide Y (NPY) reduces metabolic rate while stimulating feeding. After burn treatment, rats were injected with 2.5 µg CRF-SAP (Cat. #IT-13) into the third ventricle. Several parameters, including resting energy expenditure, NPY concentrations in the paraventricular nucleus, and CRFr-2 density were evaluated post-treatment. The results indicate that the CRFr-2 is important in maintaining hypermetabolism resulting from burn trauma.

Related Products: CRF-SAP (Cat. #IT-13)

Chance WT, Dayal R, Friend L, Sheriff S (2004) Intraventricular injection of CRF receptor 2 antisense oligonucleotide reduces burn-induced hypermetabolism. Neuroscience 2004 Abstracts 890.22. Society for Neuroscience, San Diego, CA.

Summary: Following major burn trauma, mammals exhibit a prolonged hypermetabolic response proportional to the size of the burn. The ability to control metabolic rate would likely result in better clinical management of burn patients. Our research employing a saporin-CRF conjugate to lesion CRF receptors suggested that activity at CRF receptor(R)-2 mediated increased resting energy expenditure (REE) in burned rats. In the present study we assessed whether treatment of burned rats with antisense oligonucleotides (ON) to CRF or CRF R-2 would reduce REE. Following anesthetization (ketamine/xylazine:80/15 mg/kg,), cannulae (24 ga) were implanted into the 3rd ventricle of 52 adult, male, SD rats. Two weeks later, these rats were anesthetized and subjected to a 25 sec, 30% body surface area, open flame burn (n = 30) or sham burn procedures (n = 22). Following (2-6 days) the burn trauma, either sense or antisense ONs to CRF (15 ug) or CRF R-2 (20 ug) was injected, ivt. REE (kcal/kg/24 hrs) was determined in these rats 7 and 14 days after burn by indirect calorimetry. Treatment with CRF antisense ON did not reduce REE in any groups. Burned rats given the CRF R-2 sense ON exhibited significant hypermetabolism both 7 (188±5 vs 156± 9) and 14 (201±8 vs 151±14) days post-burn, as compared to sham-burned rats. Burned rats treated with the CRF R-2 antisense ON were not significantly different from sham burned rats 7 (169±8) or 14 (167±5) days post-burn. Since the antisense treatment should decrease translation of message into protein at the receptor, these results suggest that activity at the CRF-2 receptor is necessary for expression of burn-induced hypermetabolism. Therefore, it is possible that CRF-2 receptor antagonists could be useful in treating burn-induced hypermetabolism.

Related Products: CRF-SAP (Cat. #IT-13)

Wiley RG, Lappi DA (2003) Targeted toxins in pain. Adv Drug Deliv Rev 55(8):1043-1054. doi: 10.1016/s0169-409x(03)00102-9

Summary: The authors discuss the use of ‘molecular neurosurgery’ in the study of nociception. Applications using targeted toxins, which include immunotoxins, protein-toxin conjugates, or peptide-toxin conjugates, are illustrated. The authors describe the use of these molecules as research tools, as well as their potential for therapeutics. A helpful table is included that lists neuronal surface markers and class of cells targeted for each targeted toxin. Reagents discussed: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10), OX7-SAP (Cat. #IT-02), 192-Saporin (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03), Anti-DAT-SAP (Cat. #IT-25), SP-SAP (Cat. #IT-07), Dermorphin-SAP (Cat. #IT-12), Orexin-SAP (Cat. #IT-20), CRF-SAP (Cat. #IT-13), and acetylated LDL-SAP (Cat. #IT-08).

Related Products: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10), OX7-SAP (Cat. #IT-02), 192-IgG-SAP (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03), Anti-DAT-SAP (Cat. #IT-25), SP-SAP (Cat. #IT-07), Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Orexin-B-SAP (Cat. #IT-20), CRF-SAP (Cat. #IT-13), Acetylated LDL-SAP (Cat. #IT-08)

Fox K, Wolff I, Curtis A, Pernar L, Van Bockstaele EJ, Valentino RJ (2002) Multiple lines of evidence for the existence of corticotropin-releasing factor (CRF) receptors on locus coeruleus (LC) neurons. Neuroscience 2002 Abstracts 637.9. Society for Neuroscience, Orlando, FL.

Summary: Several physiological and anatomical findings suggest that CRF acts as a neuromodulator of LC neuronal activity. However, in situ hybridization studies have failed to demonstrate the existence of CRF receptor mRNA in LC neurons, arguing against a direct effect on these neurons. Here, a combination of techniques was used to test the hypothesis that LC neurons express CRF receptors. Primers for CRF-R1 and beta-actin were generated and micropunches of the LC were subjected to RT-PCR analysis. Bands at the predicted size for each PCR product were detected in samples obtained from the LC. The presence of CRF-receptor immunolabeling in LC tissue was also examined in Western blots. This revealed a band at 52 kD, consistent with the molecular weight reported in brain and the band was absent in membranes incubated with a combination of the CRF receptor antisera and the blocking peptide. In dual labeling immunohistochemical studies, tyrosine hydroxylase (TH) immunolabeled LC neurons exhibited CRF-receptor immunolabeling and this was absent in sections that were incubated in antisera that was preabsorbed with the blocking peptide. Ultrastructural analysis also revealed co-localization of CRF-receptor immunolabeling and TH in LC dendrites. Finally, intra-LC injection of a CRF-saporin conjugate (40-60 ng in 30 nl), but not unconjugated saporin, resulted in a time dependent neuronal damage that was selective to LC neurons. The present findings provide convergent evidence for the existence of CRF receptors in LC neurons.

Related Products: CRF-SAP (Cat. #IT-13)

Maciejewski-Lenoir D, Heinrichs SC, Liu X-J, Ling N, Tucker A, Xie Q, Lappi DA, Grigoriadis DE (2000) Selective impairment of corticotropin-releasing factor1 (CRF1) receptor-mediated function using CRF coupled to saporin. Endocrinol 141:498-504. doi: 10.1210/endo.141.2.7336

Summary: Corticotropin-releasing factor 1 (CRF1) is a 41-amino acid peptide which mediates many of the body’s behavioral, autonomic, immune, and endocrine responses to stress. Reduced activation of the CRF systems plays a role in a variety of psychiatric and metabolic disease states. Maciejewski-Lenoir et al. have developed a CRF-SAP targeted toxin that can eliminate cells expressing the CRF1 but not CRF2a receptors. These data indicate that CRF-SAP (Cat. #IT-13) may be useful as a tool to examine receptor-selective impairment of CRF system function.

Related Products: CRF-SAP (Cat. #IT-13)