Effects of Pyridoxal-5′-Phosphate and Haloperidol on Synaptic Transmission in Human Colon Smooth Muscle

Abstract

1 Bogomolets National Medical University, Kyiv, Ukraine. Correspondence should be addressed to M. M. Grusha (e-mail: mishagru@stenos.kiev.ua). Vitamin B 6 (pyridoxal), pyridoxal-5′-phosphate (PyrP), and haloperidol are drugs that can significantly influence the gastrointestinal motility in humans. A modified sucrose-gap technique was used in our experiments conducted on atropinized muscle strips isolated from the circular muscle layer of visually intact regions of the human ascendens, transversum, descendens, or sigmoideum colonic tissue removed in the course of surgical interventions caused by cecum, sigmoid, or rectum cancer. Spontaneous electrical activity was recorded in 85% of the cases. Inhibitory synaptic potentials (ISP) consisted of a single “fast” component and two-component ISP (including “fast” and “slow” components) were observed in 51 and 49% of the cases, respectively. Post-ISP depolarization waves with action potentials on their crests were found in 38% on the examined muscle strips, and depolarization at the boundary between the components of two-component ISP was observed in 32% of the cases. In experiments with drug application on muscle strips, control values of the analyzed parameters were taken as 100%. After 1to 5-min-long application of PyrP (1 · 10 M), the amplitude of ISP decreased to 86 ± 4, in 6-10 min to 73 ± 6% (n = 8), in 11-15 min to 68 ± 6% (n = 7), in 16-20 min to 57 ± 5, and in 21-25 min to 46 ± 7% (n = 4). After 6to 10-min-long application of PyrP, the latency of ISP increased to 128 ± 9% (n = 7), in 11-15 min to 135 ± 2% (n = 5), and in 16-20 min to 144 ± 8% (n = 4). Simultaneously, PyrP significantly increased the ISP duration (n = 8) and suppressed post-ISP depolarization waves with action potentials on their crests and depolarizations at the boundary between two components of complex ISP. Pyridoxal (1 · 10 M) less effectively than PyrP decreased the ISP amplitude. After 11to 15-min-long application of haloperidol (1 · 10 M), the amplitude of ISP decreased to 67 ± 8, in 16-20 min to 50 ± 7% (n = 7), in 21-25 min to 34 ± 7, in 26-30 min to 25 ± 7% (n = 6), in 36-40 min to 3 ± 2% (n = 5), and after 46to 50-min-long applications the amplitude dropped to zero (n = 5). After 16to 20-min-long application of haloperidol, the time of half-decay of ISP decreased to 74 ± 3 % (n = 6), spontaneous electrical activity and post-ISP depolarization waves with action potentials disappeared (n = 7), as well as depolarizations interposed between the components of two-component ISP did. The latency of ISP increased to 129 ± 2% (n = 5) in 26-30 min. The tested drugs can be considered effective modulators of synaptic transmission in the colonic smooth muscles.