dynorphins and Carcinoma-256--Walker

Rats implanted with the Walker-256 (W-256) tumor exhibit marked anorexia that is most apparent at night. In this model, the hypothalamic kappa opioid system was examined for deficits that might contribute to this tumor-induced anorexia. In anorexic tumor-bearing rats (TBR), nocturnal levels of ir-DYN-8 were significantly reduced in the hypothalamus, but ir-DYN-17 levels were not. Accumulation of 3H-etorphine or 3H-ethylketocyclazocine, a putative ligand for the kappa receptor subtype, was not increased in the hypothalamus of the TBR, as might have been expected if there were less endogenous dynorphin to occupy the opioid receptors in this region. In vitro binding assays with 3H-ethylketocyclazocine indicated that dynorphin depletion in the TBR was not sufficient to increase the numbers of kappa opioid receptors in the hypothalamus. Also, the sensitivity of kappa opioid receptors involved in feeding was not altered in the TBR as indicated by an intact feeding response to ketocyclazocine. In summary, the marginal deficits of hypothalamic dynorphin in W-256 tumor-bearing rats that coincide with the phase of tumor-induced anorexia may contribute to the reduction in food intake.

Topics: Animals; Anorexia; Carcinoma 256, Walker; Circadian Rhythm; Cyclazocine; Dynorphins; Eating; Ethylketocyclazocine; Feeding and Eating Disorders; Hypothalamus; Male; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa

Walker-256 tumor tissue was removed from rats on day 8 of tumor growth. An acidified methanol extract of the tumor tissue was assayed for immunoreactive (ir) dynorphin-A 1-17 (DYN-17) and ir-dynorphin-A (DYN-8). Levels of ir-DYN-17 and ir-DYN-8 were nearly 4-and 8-fold higher, respectively, in tumors versus normal muscle. However, tumor homogenates did not exhibit specific 3H-naloxone binding. These results indicate that although the Walker-256 carcinosarcoma may produce opioids, it is unlikely that these ectopic substances have direct opioid actions on the tumor itself.

Topics: Animals; Carcinoma 256, Walker; Dose-Response Relationship, Drug; Dynorphins; Endorphins; Hormones, Ectopic; Male; Muscles; Naloxone; Peptide Fragments; Rats; Rats, Inbred Strains; Receptors, Opioid

Rats bearing the Walker-256 (W-256) tumor display an anorexic profile which resembles that of normal animals forced to drink 2% NaCl [2,24], a regimen which depletes neurohypophyseal dynorphin-A (DYN) [3,9]. As expected, the naloxone reversible feeding induced by 2-deoxy-D-glucose (2-DG) was attenuated (36%) in the W-256 tumor bearing rats (TBR). Interestingly, immunoreactive (ir) levels of dynorphin-A 1-17 (DYN-17) and its postulated breakdown product, dynorphin-A 1-18 (DYN-8), were also reduced in the neurohypophysis of W-256 TBR by 42 and 50%, respectively. However, ir-DYN levels were not reduced in TBR in those brain regions which are probably involved in the regulation of appetite (e.g., hypothalamus). 2-DG itself did not consistently affect ir-DYN levels in any tissue for either controls or TBR. The ratio of DYN-8 to DYN-17 did not change in response to any treatment, including the depletion of both peptides from the NIL of TBR. In summary, the present data do not support DYN depletion as being a factor which contributes to the anorexia of the W-256 TBR.

Topics: Animals; Anorexia; Brain Chemistry; Carcinoma 256, Walker; Dynorphins; Feeding and Eating Disorders; Male; Peptide Fragments; Pituitary Gland, Posterior; Rats; Rats, Inbred Strains