FOR III]MBESIN WIlll ASSOCIATEDTYROS IO, D. CIRILLO, L. GANDINO, G. GAUl Sciences &Oncology, University o"
also known foe i t s potent mitogen (P-Tyr) antibodies have been st r known growth factors such as E 5 Kd cell surface protein (p115) tl n stimulation of quiescent cells• the mitogenic effect induced b ~ylation of p115 was detectable mi~ scribed foK the ~ d i n g of bombes antibodies bound ~OI-TYr4-bombesil e kinase a c t i v i t y enhanced by bom intact l i v e c( -gast~i,LreieaSing:peptide (GRP), bound t# intac. ;s-linking experiments performed with disuccinimidyl suberate s~ (I :ed to two cell surface proteins with apparent m.w. (of 115 Kd ; p115 participates in the structure and function of the tl surfac~ msphotyrosine antibodies did also ~ecognize a p~otei otein of 115 m SCLC lines producing bombesin, but not in a non-pr )~oducer '~ Lted SCLC did bind to bombesin immobilized on Sepha~( ose and b, ;ence of radiolabeled ATP and Mn ions• As in the case of the p ;oblast, the SCLC p115 was phospho~ylated in an limmuno, mmunocomplex k life the presence of exogenous bombesin in the asseLy foe ac =thesis of autocrine activation of bombesin r e c e p t o r sin human
artment ZHAVIORAL EFFECTS OF BOMBESIN A. Cowan, Depa BEH ~ol o f Medicine, P h i l a d e l p h i a , PA 19140, U.S..A. School
CTIYITY NALDINI ical School.
mu~ine 3T3 fib~oblasts a employed to ~ecognize t • In Swiss 3T3 fibroblast hospho~ylated on tyrosine of phospho~ylation was do measured by 3H-thymidi addition of bombesin and i ~eceptor. Immunocomplexes f i c and saturable manne~ a e~mo~e, the bombesin anal ~-p~ecipitated with p115. P was found to be covalent These data strongly sugge oc bombesin. rylated at tyrosine, in fo e. This p115 from deterge o~ylated at tyrosine in t mmunoprecipitated from mou However, the latte~ did n se observations f u l f i l l t ung carcinoma cells.
cerebroventricularly ombesin (given intracere The most obvious response o f mice and r a t s to bo Immediate and incessant i.c . v . ) is a remarkable display of grooming and scratching. minant behavior. Th atching of the head and neck area with the hiindpaws is the predomina scratchin( :ratching/grooming in potent inducer of scratch ~ent studJ studies have shown that bombesin is a Do present Thus, guinea pigs, rabbits and monkeys quickly respond several other species ass well. small doses of centrall, y administered bombesin with behaviors which are suggestive of The overt behavior of frogs and pigeons appoears to be unchanges in skin sensation. In mice, bombesin affected by the peptide, , at least under our experimental conditions. nt as a scratch inducer by i.c.v. (A50=O.OIO pg, that is, 6 pmol is essentially equipotent Scratching can be eli Scrat and intrathecal (i.th.) (A50=0.019 pg) routes of administration• is required. do ited by i.p. injection but a dose 6800 times greater than the i.c.v, dose In rats, tolerance does not develop to the scratching when bombesin is chronically infu scratching ic minipump, implanted s.c. The robust and uniform unif ed i.c.v, from an osmotic in this andard, submaximal dose of bombesin (O.lO pg, z.c.v.) i. behavior evoked by a standard i b o m b e s i n agents, e. ellent endpoint when searching for novel antibom species provides an excel robes. Central inje bombesin antagonists forr use as physiological and pharmacological probe tested in sma a ion of bombesin to rats increases locomotor activity when the animals are in Res. 193: 209, 1980; Schulz et al., Brain Res • 304: 37~ 1984) cages (Pert et al., Brain r e a t e d with fluphenThe increased locomotionn can be antagonized if the animals are pretreat The present studies have she azine or haloperidol, suuggesting involvement of dopamine. ncreases, locomotor that bombesin (0.062-6.22 nmoles, i.c.v.) decreases, rather than increas )hotobeam activity met activity over 2 hr when single mice are monitored by an infrared photob given into t w Bombesin has previously been shown to have an antinociceptive action, when TF periaqueductal gray of rats, in hot plate and tail flick tests (Pert et al., 1980). present work has revealed ed that bombesin also has antinociceptive proper ~erties in the mous (acetic acid) stretchincg test. Evidence for an overlap in bombesin and opiate pharmacc ogy derives from the di scovery that kappa opioid agonists selectively attenuate a bombesJ induced scratching in rats. It follows, then, that kappa agonists may be drugs of choi for the relief of pain and itch associated with human lung small cell carcinoma, c a condition in which bombesinn has been implicated. (Supported by DA 03681 from f NIDA).