Gmerek D E, Ryan J P, Cowan A
Eur J Pharmacol. 1985 Aug 15;114(2):175-80. doi: 10.1016/0014-2999(85)90625-9.
Intracerebroventricular (i.c.v.) injection of either morphine or bombesin to rats inhibits intestinal transit of an intraduodenally administered radiochromium marker. In this work, we show that tolerance develops to this effect of bombesin after i.c.v. infusion of the peptide (0.5 micrograms/h for 4 days via an s.c. implanted Alzet 2001 osmotic minipump). Tolerance also develops to the inhibition of intestinal transit associated with i.c.v. morphine after s.c. injections of morphine. Bombesin-induced delay of transit is not attenuated by naltrexone (10 mg/kg, s.c.), a standard narcotic antagonist. Nevertheless, two-way cross-tolerance develops between bombesin and morphine in this system. This is a surprising result since both bombesin and morphine are believed to act on different receptors and cause opposite effects on intestinal motility in rats.
向大鼠脑室内（i.c.v.）注射吗啡或蛙皮素会抑制十二指肠内给予的放射性铬标记物在肠道中的转运。在本研究中，我们发现，通过皮下植入的Alzet 2001渗透微型泵以0.5微克/小时的速度脑室内输注该肽4天之后，对蛙皮素的这种作用会产生耐受性。皮下注射吗啡后，对与脑室内注射吗啡相关的肠道转运抑制也会产生耐受性。纳曲酮（10毫克/千克，皮下注射）是一种标准的麻醉拮抗剂，它不会减弱蛙皮素引起的转运延迟。然而，在该系统中，蛙皮素和吗啡之间会产生双向交叉耐受性。这是一个令人惊讶的结果，因为人们认为蛙皮素和吗啡都作用于不同的受体，并对大鼠的肠道运动产生相反的影响。
