Kraly F S, Katz J B, Burchard A E, Case C, Gabriel V A, Lanz T A, Mikkelsen M E, Sokol M B
Department of Psychology, Colgate University, Hamilton, NY 13346, USA.
Physiol Behav. 1998 Aug;65(1):105-13. doi: 10.1016/s0031-9384(98)00144-9.
A role for endogenous histamine and histamine receptor subtypes in mediating the inhibition of eating induced by intragastric (i.g.) hypertonic NaCl was examined in adult male Sprague-Dawley rats surgically equipped with a chronic gastric catheter. The i.g. infusion of 2 mL 900 or 1,800 mOsm/kg of NaCl inhibited: 1) ingestion of pellets in rats eating after 24-h food deprivation; and 2) ingestion of cookies in rats eating without prior deprivation. The H1 receptor antagonists dexbrompheniramine (DXB; 1 mg/kg) and pyrilamine (PYR; 4 mg/kg) did not attenuate the inhibitory effects of i.g. 900 or 1,800 mOsm/kg of NaCl for rats eating pellets and for rats eating cookies. The H2 antagonists cimetidine (CIM; 16 mg/kg) and metiamide (MET; 16 mg/kg) attenuated the inhibitory effects of i.g. 1,800 mOsm/kg of NaCl upon ingestion of cookies, but intracerebroventricular (i.c.v.) infusion (through a chronic indwelling cannula) of 100 microg of CIM did not mimic this effect of intraperitoneal (i.p.) CIM. The i.p. CIM failed to attenuate the inhibition of eating cookies produced by i.p. octapeptide of cholecystokinin (CCK-8; 3 microg/kg). The H3 antagonist thioperamide (TH; 10 mg/kg i.p.) and the H3 agonist R-alpha-methylhistamine (RAM; 3 mg/kg i.p.) did not alter the inhibitory effect of i.g. 1,800 mOsm/kg of NaCl for rats eating cookies. Combined treatments of systemic DXB plus CIM, and DXB plus CIM plus thioperamide (TH) did not reverse the inhibitory effects of i.g. 1,800 mOsm/kg of NaCl upon ingestion of cookies. Finally, i.p. DXB, but not CIM, attenuated the ability of i.g. 900 mOsm/kg of NaCl to increase water intake; conversely, i.p. CIM, but not DXB, attenuated the ability of i.g. 900 mOsm/kg of NaCl to inhibit eating of cookies. These findings demonstrate a double dissociation of effects upon ingestive behavior: H1, but not H2, antagonism attenuates the effect of i.g. hypertonic NaCl on water intake, whereas H2, but not H1, antagonism attenuates the inhibition of eating produced by i.g. hypertonic NaCl. These results demonstrate that different subtypes of peripheral and/or central histamine receptors contribute to different behavioral consequences of postprandial gastrointestinal osmotic loads in rats.
在成年雄性斯普拉格-道利大鼠身上，通过手术植入慢性胃导管，研究内源性组胺及其受体亚型在介导胃内（i.g.）高渗氯化钠诱导的进食抑制中的作用。胃内注入2 mL 900或1800 mOsm/kg的氯化钠可抑制：1）24小时禁食后进食的大鼠对颗粒的摄取；2）未预先禁食的大鼠对饼干的摄取。H1受体拮抗剂右溴苯那敏（DXB；1 mg/kg）和吡苄明（PYR；4 mg/kg）并未减弱胃内注入900或1800 mOsm/kg氯化钠对摄取颗粒的大鼠和摄取饼干的大鼠的抑制作用。H2拮抗剂西咪替丁（CIM；16 mg/kg）和甲硫米特（MET；16 mg/kg）减弱了胃内注入1800 mOsm/kg氯化钠对饼干摄取的抑制作用，但脑室内（i.c.v.）注入（通过慢性留置套管）100 μg的CIM并未模拟腹腔内（i.p.）CIM的这种作用。腹腔内注射CIM未能减弱腹腔内注射胆囊收缩素八肽（CCK-8；3 μg/kg）对饼干摄取的抑制作用。H3拮抗剂硫代胡椒嗪（TH；10 mg/kg腹腔注射）和H3激动剂R-α-甲基组胺（RAM；3 mg/kg腹腔注射）并未改变胃内注入1800 mOsm/kg氯化钠对摄取饼干的大鼠的抑制作用。全身性DXB加CIM以及DXB加CIM加硫代胡椒嗪（TH）的联合治疗并未逆转胃内注入1800 mOsm/kg氯化钠对饼干摄取的抑制作用。最后，腹腔内注射DXB而非CIM减弱了胃内注入900 mOsm/kg氯化钠增加水摄入的能力；相反，腹腔内注射CIM而非DXB减弱了胃内注入900 mOsm/kg氯化钠抑制饼干摄取的能力。这些发现表明对摄食行为的影响存在双重解离：H1而非H2拮抗剂减弱胃内高渗氯化钠对水摄入的影响，而H2而非H1拮抗剂减弱胃内高渗氯化钠对进食的抑制作用。这些结果表明外周和/或中枢组胺受体的不同亚型促成了大鼠餐后胃肠道渗透压负荷的不同行为后果。
