Opioid and Opiate Immunoregulatory Processes.

The discovery of the ability of the nervous system to communicate through "public" circuits with other systems of the body is attributed to Ernst and Berta Scharrer, who described the neurosecretory process in 1928. Indeed, the immune system has been identified as another important neuroendocrine target tissue. Opioid peptides are involved in this communication (i.e., neuroimmune) and with that of autoimmunoregulation (communication between immunocytes). The significance of opioid neuropeptide involvement with the immune system is ascertained from the presence of novel δ, µ., and κ receptors on inflammatory cells that result in modulation of cellular activity after activation, as well as the presence of specific enzymatic degradation and regulation processes. In contrast to the relatively uniform antinociceptive action of opiate and opioid signal molecules in neural tissues, the presence of naturally occurring morphine in plasma and a novel µ3 opiate-specific receptor on inflammatory cells adds to the growing knowledge that opioid and opiate signal molecules may have antagonistic actions in select tissues. In examining various disorders (e.g., human immunodeficiency virus, substance abuse, parasitism, and the diffuse inflammatory response associated with surgery) evidence has also been found for the involvement of opiate/opioid signaling in prominent mechanisms. In addition, the presence of similar mechanisms in man and organisms 500 million years divergent in evolution bespeaks the importance of this family of signal molecules. The present review provides an overview of recent advances in the field of opiate and opioid immunoregulatory processes and speculates as to their significance in diverse biological systems.

Cyclic nitric oxide release by human granulocytes, and invertebrate ganglia and immunocytes: nano-technological enhancement of amperometric nitric oxide determination.

BACKGROUND: Various tissues from vertebrates and invertebrates respond to external signal molecules by rapid release of nitric oxide (NO) mediated by constitutive nitric oxide synthase. MATERIAL/METHODS: Invertebrate immunocytes were collected from maintained stock and human granulocytes were isolated from leukocyte-enriched blood obtained from the Long Island Blood Services. The invertebrate ganglionic tissue was either extracted or exposed for ex vivo and in vivo evaluation. Nitric oxide release was measured using a newly developed NO-selective nanoprobe, exhibiting enhanced sensitivity. RESULTS: Evaluation of NO release from the pedal ganglia of the marine bivalve, Mytilus edulis, demonstrated in vitro release of NO that fluctuated from 969 to 1003 pM, with a mean change in NO of 35 pM/cycle and a mean cycle time of approximately 4 minutes. Basal release of NO/cycle from the ganglia in vivo was increased significantly to approximately 65 pM (P<0.05) with an increase in cycle time to approximately 7 minutes. Exposure of the ganglia to morphine in vivo resulted in a significant increase in NO release and a lack of NO pulsations. The fluctuation in NO release from immunocytes of Mytilus edulis was approximately 27 pM per cycle with a cycle time of 4 minutes whereas human granulocytes release fluctuated approximately 23 pM with a cycle time of 6 minutes. CONCLUSIONS: These data demonstrate that basal release of NO from various tissues is released in a cyclic manner and the cycle time and magnitude is subject to regulation by external stimuli.

Direct assessment and diminished production of morphine stimulated NO by diabetic endothelium from saphenous vein.

AIM: To directly measure in real time basal and stimulated levels of NO released from human saphenous vein endothelium and to quantify the expression of the mu opiate receptor, which has been linked with NO release. METHODS: Saphenous vein segments from patients with type 2 diabetes (n=12) and patients without diabetes (n=8) were obtained. The release of NO was measured directly from the endothelium using a NO-specific amperometric probe. N(Omega)-nitro-L-arginine methyl ester (L-NAME, 0.1 mmol/L), a NO synthase (NOS) inhibitor, or morphine (1 mumol/L), a stimulant, was administered and the measurements were repeated. Values were reported relative to the mean initial measurement of NO release from diabetic endothelium, which was defined as the relative zero level of NO release. A RT-PCR was then performed on the endothelium to measure mu opiate receptor expression. RESULTS: Diabetic patients (n=12) showed a relative and significantly diminished basal level of released NO, (0.049+/-0.012) nmol/L, compared with non diabetic patients (n=8), (0.42+/-0.12) nmol/L (P<0.05). Application of L-NAME to nonstimulated tissues resulted in no change in NO release from the diabetic group and a decrease in NO release of (0.21+/-0.09) nmol/L from the non diabetic group (P<0.05). Morphine stimulation of the diabetic endothelium resulted in a lower peak and shorter duration of NO release compared to the non-diabetic tissue, (21+/-6) nmol/L vs (38+/-4) nmol/L and (7.3+/-1.4) min vs (12.2+/-2.2) min, respectively (P<0.01). Lastly, evaluation of the mu opiate receptor expression was found to be diminished in the diabetics by 59.1 %. CONCLUSION: Maturity-onset diabetes attenuates both the constitutive basal and morphine stimulated NO release from human saphenous vein endothelium. In this study, after NOS inhibition, the actual basal NO release in diabetes was negligible. One explanation for the impaired capacity of diabetic endothelium to release NO was the diminished mu opiate receptor that was seen in diabetic endothelium.