ABSTRACT
Many reports suggest that neurotensin (NT) in the gastrointestinal tract may play a possible role as a neurotransmitter, a circulating hormone, or a modulator of motor activity. NT exerts various actions in the intestine; it produces contractile and relaxant responses in intestinal smooth muscle. This study was designed to investigate the effect of NT on motility of antral circular muscle strips in guinea-pig stomach. To assess the role of Ca2+ influx in underlying mechanism, slow waves were simultaneously recorded with spontaneous contractions using conventional intracellular mircoelectrode technique. At the concentration of 10-7 M, where NT showed maximum response, NT enhanced the magnitude (863 +/- 198%, mean +/- SEM, n = 13) and the frequency (154 +/- 10.3%, n = 11) of spontaneous contractions. NT evoked a slight hyperpolarization of membrane potential, tall and steep slow waves with abortive spikes (278 +/- 50%, n = 4). These effects were not affected by atropine (2 micrometer), guanethidine (2 micrometer) and tetrodotoxin (0.2 micrometer). NT-induced contractile responses were abolished in Ca2+-free solution and reduced greatly to near abolition by 10 micrometer of verapamil or 0.2 mM of CdCl2. Verapamil attenuated the effects of NT on frequency and amplitude of the slow waves. Taken together, these results indicate that NT enhances contractility in guinea-pig gastric antral circular muscle and Ca2+ influx through the voltage-operated Ca2+ channel appears to play an important role in the NT-induced contractile mechanism.