DEVELOPMENTAL-CHANGES IN THE RESPONSE OF RAT ISOLATED DUODENUM TO NICOTINE

Developmental changes in the response to ganglionic stimulants, nicoti ne and dimethylphenylpiperazinium, were investigated in rat isolated d uodenum by recording isotonic mechanical activity. The duodenal respon se to nicotine/dimethylphenylpiperazinium (3 x 10(-7) to 10(-3) M) in neonatal rats was contraction, which was blocked by hexamethonium, tet rodotoxin and hyoscine. The response to nicotine/dimethylphenylpiperaz inium (10(-6) to 10(-4) M) in the adult duodenum was relaxation, which was blocked by tetrodotoxin and hexamethonium, but by neither guaneth idine nor hyoscine. The transition of the response to nicotine/ dimeth ylphenylpiperazinium from contraction to relaxation occurred at around the 3rd postnatal week. Nicotine-induced relaxation of adult duodenum was significantly inhibited by preincubation with alpha-chymotrypsin, a proteolytic enzyme, and a combination of nucleotide pyrophosphatase and 8-phenyltheophylline, a P-1 purinoceptor antagonist. Nicotine-ind uced relaxation was desensitized by alpha,beta-methylene ATP, a stable P-2X purinoceptor agonist. These results suggest that the contractile response of isolated duodenum to nicotine is mediated through choline rgic transmission in neonatal rats and the relaxant response is mediat ed through non-adrenergic, non-cholinergic transmission, which involve s both peptidergic and purinergic transmission, in adult rats.