cyprodime and binaltorphimine

Previously, we reported that central administration of bombesin, a stress-related peptide, elevated plasma levels of catecholamines (noradrenaline and adrenaline) in the rat. The sympatho-adrenomedullary system, which is an important component of stress responses, can be regulated by the central opioid system. In the present study, therefore, we examined the roles of brain opioid receptor subtypes (µ, δ, and κ) and nociceptin receptors, originally identified as opioid-like orphan receptors, in the bombesin-induced activation of central sympatho-adrenomedullary outflow using anesthetized male Wistar rats. Intracerebroventricularly (i.c.v.) administered bombesin-(1 nmol/animal) induced elevation of plasma catecholamines was significantly potentiated by pretreatment with naloxone (300 and 1000 µg/animal, i.c.v.), a non-selective antagonist for µ-, δ-, and κ-opioid receptors. Pretreatment with cyprodime (100 µg/animal, i.c.v.), a selective antagonist for µ-opioid receptors, also potentiated the bombesin-induced responses. In contrast, pretreatment with naltrindole (100 µg/animal, i.c.v.) or nor-binaltorphimine (100 µg/animal, i.c.v.), a selective antagonist for δ- or κ-opioid receptors, significantly reduced the elevation of bombesin-induced catecholamines. In addition, pretreatment with JTC-801 (30 and 100 µg/animal, i.c.v.) or J-113397 (100 µg/animal, i.c.v.), which are selective antagonists for nociceptin receptors, also reduced the bombesin-induced responses. These results suggest that brain µ-opioid receptors play a suppressive role and that brain δ-, κ-opioid, and nociceptin receptors play a facilitative role in the bombesin-induced elevation of plasma catecholamines in the rat. Thus, in the brain, these receptors could play differential roles in regulating the activation of central sympatho-adrenomedullary outflow.

Topics: Adrenal Medulla; Animals; Bombesin; Brain; Catecholamines; Morphinans; Naloxone; Naltrexone; Nociceptin Receptor; Rats; Receptors, Opioid; Sympathetic Nervous System

The head kidney is the main lymphopoietic organ of teleost fish. It is the source of leukocytes inhabiting the peritoneal cavity during an experimental peritoneal inflammation (Gruca et al., Folia Biol.-Kraków, 1997, 44, 137-142). The number of elicited peritoneal leukocytes is significantly lower in the goldfish with concomitant morphine injection than in their counterparts injected with the irritant only. Morphine may act directly on the head kidney leukocytes, as they are equipped with the selective naloxone-binding sites (Chadzińska et al., Arch. Immunol. Ther. Exp., 1997, in press). Further characterization of these opioid receptors (by radioligand binding techniques) indicates that the goldfish head kidney leukocytes possess at least two different opiate-binding sites: the [3H]naloxone binding site with a KD = 87 +/- 2.1 nM and Bmax = 298 +/- 15 fmol/mg protein; and the second, the [3H]naltrindole binding site with a KD = 37 +/- 5.5 nM and Bmax = 1,172 +/- 220 fmol/mg protein. The competition experiments with delta- (naltrindole), kappa- (nor-binaltorphimine) and mu- (cyprodime, naltrexone) selective ligands suggest that the naloxone-binding site is similar to mu 3 receptors described by Stefano et al. (Proc. Nat. Acad. Sci. USA, 1993, 90 11099-11103). Low affinity binding of selective ligands excludes the presence of neuronal-type mu- and delta-opioid receptors on goldfish leukocytes.

Topics: Animals; Binding Sites; Goldfish; Leukocytes; Morphinans; Morphine; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid, delta; Receptors, Opioid, mu