The effects of neurotensin (NT) on the mechanical activity of the smooth muscle and membrane currents of enzymatically-dispersed single smooth muscle cells of guinea-pig intestine were investigated by the isometric tension recording method and the whole-cell patch clamp technique, respectively. 2. NT (0.3-670 nM) produced an initial relaxation followed by a contraction in segment preparations of the jejunum and ileum. Atropine (0.2 microM) abolished the contraction. In 30% of ileal segments, NT produced a slowly-developed contraction in the presence of atropine. The atropine-resistant contraction was insensitive to tetrodotoxin (TTX, 0.2 microM). The relaxant effect of NT was unaffected by TTX (0.2 microM) and guanethidine (2 microM), but markedly reduced or abolished by apamin (67 nM). 3. In segment preparations of the colon and rectum, NT produced a biphasic response, similar to that in the small intestine, or a triphasic one (relaxation, contraction and relaxation). The contractile effect of NT was affected neither by atropine (0.2 microM) nor by TTX (0.2 microM). The first relaxation in response to NT was similar in pharmacological properties to that in the small intestine. 4. Responses to NT in longitudinal muscle strips were similar to those in segment preparations. The taenia caecum responded to NT with a contraction alone and the effect was unaffected by atropine (0.2 microM) and TTX (0.2 microM). 5. NT had little or no effect on the mechanical activity in the circular muscle of the small intestine. In the circular muscle of the large intestine, NT had a weak inhibitory effect on the spontaneous activity which was followed by a small rise in muscle tone. Apamin (67 nM) converted the biphasic response to a contraction. 6. In cells dialysed with a KCl-based solution under voltage clamp at 0 mV, NT (5 microM) produced a brief, outward current in a very small fraction of cells (4 out of 40 cells). When cells were dialysed with a CsCl-based solution under voltage clamp at -50 or -60 mV, no current response to NT (5 microM) was observed in all 37 cells, but NT increased inward Ca2+ currents evoked upon depolarization. 7. From these results, it appears that there is a regional difference in the mode of action of NT to contract and relax the smooth muscle of guinea-pig intestine, and NT acts on its receptors on the smooth muscle to enhance activation of voltage-dependent Ca2+ channels, which underlies the slow contraction in the longitudinal muscle of the intestine.
