Study on the mechanism(s) of action of the shake-inducing effect of putrescine

176

PharmacologicalResearch Communication~ VoL 2~ Supplement ~ 1988

SIIJDY ON THE MECHANISM(S) OF ACTION OF ~

SHAKE-INDUCING EFFECT OF

PUTRESCINE

S. Genedani, M. Bernardi, S. Tagliavini, ~A. Botticelli and A. Bertolini Institutes of Pharmacology and IPathological Anatomy, University of Modena Key words: Putrescine, Polyamines, Net-do E shakes Putrescine, the ubiquitous precursor of polyamines, dose-dependently induces a typical wet-do E shame response when intraperitoneally naive rats, in a dose range of 100-300mg/kg

(i.p.) injected to

(Genedani et al., 1987).

The

aim of the present study was to investigate the site and mechanism(s) of action of this effect. The intracerebroventricular (i.c.v.) injection of putrescine in a dose-range of 100-2500 rm~les/rat (=16-~00 mg/kg) did not evoke wet-dog shakes. Pretreatment with aminoEuanid/ne (60 mE/kg i.p.),an inhibitor of the oxidative metabolism of putrescine, did not affect the snakin~ response to putrescine i.p. injected 2 h later. The acetylated metabolite of putrescine, acetylputrescine,

i.p. injected at up to ~00 mg/kg,

induced no wet-doE shake. The i.c.v, injection of fractions obtained by ultrafiltration of the serum of rats i.p. treated with putrescine (~00 mE/ kg) evoked no, or negliEible, shaking behavior. The i.p., but not the i.c.v. injection of putrescine markedly increased brain vascular permeability, as histologically assessed by PAS method and I g detection. Finally~ the shaking behavior induced by i.p. putrescine is antagonized only by morphine which also prevents the increase in brain vascular permeability, and is not affected by atropine, bicuculline, chlorphen/ramine,cimetidine,

methysergide,

naloxone, norepinepbrine. These data indicate that the shake-inducing effect of putrescine:

(i) is associated with an increased permeability of brain

vessels; (ii) can be induced only after peripheral administration, but is not due to a putrescine metabolite;

(iii) is antaEonizedbymorphine.

RE~ERENCES Genedani S., Bernardi M., Tagliavini S., Botticelli A. and Bertolini A. (1987) Pharmacol. Toxicol. 61 : 224-227