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Previous work had shown that interleukin 1 (IL-1), after a long period of treatment, stimulates fi-endorphin release and potentiates the effects of secretagogues in

Previously, GRP receptors were characterized in small cell lung cancer cells and here non-small cell lung cancer (NSCLC) cells were investigated: (1251-Tyr4) bombesin (BN) or lZ51-GRP bound with high affinity to NCLH720 (lung carcinoid) and NCI-HI 299 (large cell carcinoma) cells. Binding was specific, time dependent, and saturable. Specific (1251-Tyr4)BN binding to NCI-HI299 cells was inhibited with high affinity by GRP, BN, CRP'"27, (D-Phe6)BNG13methyl ester, moderate affinity by NMB, and low affinity by GRP1-I6. BN (10 nM) transiently elevated cytosolic calcium in a dose dependent manner. BN caused translocation of protein kinase C from the cytosol to the membrane and the translocation caused by BN was reversed by The GRP receptor has been cloned and is comprised of 7 hydrophobic domains and 384 amino acid residues [15,161. It has 56% sequence homology with the NMB receptor which binds NMB but not GRP with high affinity [171.Recently it was found that SCLC cells have NMB immunoreactivity and mRNA [18,193 and NMB receptors. NMB elevates the cytosolic Ca2+ and stimulates the growth of SCLC cells [20]. The actions of NMB are reversed with low f i nity by (D-Argl, D-Pro2, D -T~P~,~, Leu1') substance P but not GRP receptor antagonists.GRP receptors have also recently been found on other tumor cell lines including breast cancer and prostate caner [21,221. Also, GRP immuno-

Previous work has shown that corticotropin releasing factor, vasoactive intestinal peptide, phorbol ester, and forskolin cause the secretion of adrenocorticotropic hormone and ,3-endorphin from the AtT-20 mouse pituitary cell line. Human recombinant interleukin la and 1(3 also stimulated adrenocorticotropic hormone and (3-endorphin secretion from AtT-20 cells in a time-and dose-related manner. The effect appeared only after pretreatment with interleukin 1 (IL-I) for at least 18 hr and was maximum at 24 hr. After pretreatment of the cells over a period of time with IL-1, the secretion induced by corticotropin releasing factor and vasoactive intestinal peptide was increased in more than an additive manner. The enhancement of corticotropin releasing factorinduced (-endorphin release produced by IL-1 was apparent after 12 hr and reached a maximum at 24 hr. IL-1 did not affect forskolin-induced cAMP generation but enhanced the effect of forskolin on 3-endorphin secretion. This suggests that IL-1 does not induce adenylate cyclase and that forskolin causes the secretion of (3-endorphin by a mechanism independent of cAMP. IL-1 enhanced phorbol ester-induced (3-endorphin secretion. After prolonged treatment with phorbol ester (an activator ofprotein kinase C), the secretion induced by phorbol ester was abolished as well as the enhancement induced by IL-1. However, prolonged treatment with phorbol ester had no effect on IL-i-induced (3-endorphin secretion. These observations suggest that IL-i enhances peptide-generated secretion of (3-endorphin by inducing protein kinase C.Interleukin 1 (IL-1) is a polypeptide lymphokine (molecular mass of 17.5 kDa) produced by numerous cell types including macrophages, fibroblasts, and astrocytes (1). There are two distinct IL-1 genes expressing IL-1 activities, IL-la and IL-1p. Although IL-la and IL-1,B have less than 30% amino acid homology, they interact with the same receptors (2). IL-1 has a broad spectrum of biological activities as well as an important role in modulation of the immune responses and inflammation (3). It produces fever, somnolence, anorexia, and elevation of acute-phase proteins. It The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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