II. Regulation of gastrointestinal function by multiple opioid receptors

Burks, Thomas F.; Fox, Deborah A.; Hirning, Lane D.; Shook, J E; Porreca, Frank

doi:10.1016/0024-3205(88)90410-9

Cited by 57 publications

(15 citation statements)

References 22 publications

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“…Among all the peptides analysed, oxytocin, CRF and bombesin administered into the cisterna magna exhibited hyposecretory properties on distension-stimulated acid secretion while vasopressin, opioid peptides and somatostatin failed to modify such a response, in accordance with previous observations on other experimental models (Burks et al 1988;Esplugues et al 1992;Martínez et al 1995;Taché et al 1981).…”

Section: Figsupporting

confidence: 90%

Role of central oxytocin in the inhibition by endotoxin of distension-stimulated gastric acid secretion

Calatayud

Quintana

Esplugues³

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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The gastric acid hyposecretory state associated with endotoxemia is mediated by a nervous reflex involving the central nervous system. The aim of the present study was to analyse the central effects of different peptides on distension-stimulated gastric acid secretion and the endogenous role of such peptides on the hyposecretory effects of endotoxin. The effect of an intracisternal (i.c.) administration of oxytocin, vasopressin, corticotropin releasing factor (CRF), bombesin, somatostatin and the opioid receptor agonist BW443C or an intravenous (i.v.) injection of a small dose of endotoxin on distension-stimulated gastric acid secretion was studied in the continuously perfused stomach of anaesthetised rats. In some animals, specific receptor antagonists for oxytocin (Compound VI [d(CH2)5, Tyr(Me)2, Thr4, Tyr-NH2(9)]-OVT, 0.01-1 microg/rat), vasopressin (des-Gly9-[beta-Mercapto-beta,beta-cyclopentamethylene-propiony l1, O-Et-Tyr2, Val4, Arg8]-VP, 20 microg/rat), CRF (alpha-helical CRF [9-41], 50 microg/rat) or bombesin (D-Phe12-Bombesin, 20 microg/rat) were administered i.c. before endotoxin. Distension-stimulated acid secretion was significantly inhibited by central oxytocin (0.2, 2 or 4 nmol/rat, 45+/-16%, 69+/-10% and 79+/-5% reduction, respectively), CRF (0.5, 1 or 2 nmol/rat, 52.2+/-15.6%, 74.3+/-9.1% and 93.2+/-1.6% reduction, respectively) and bombesin (2 nmol/rat, 79.1+/-5.8% reduction). The hyposecretory effect induced by endotoxin (5 microg/kg, 60.2+/-2.3% reduction) was reversed in a dose-dependent manner by pretreatment with the oxytocin receptor antagonist (0.01, 0.1 and 1 microg/rat, 65.2+/-14.4%, 88.0+/-22.5% and 112.4+/-25.2% of control response, respectively) while the vasopressin (20 microg/rat), CRF (50 microg/rat) or bombesin (20 microg/rat) receptor antagonists had no effect. The present results support a role for the endogenous release and action in the central nervous system of oxytocin in the inhibitory effect of endotoxin on gastric acid secretion.

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Section: Figsupporting

confidence: 90%

Role of central oxytocin in the inhibition by endotoxin of distension-stimulated gastric acid secretion

Calatayud

Quintana

Esplugues³

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…It has subsequently been shown that morphine delays gastrointestinal (GI) transit in the mouse and the rat [28], as well as in humans [29,30]. We have shown that C3HeB/FeJ mice implanted with slow-release morphine pellets, or with osmotic mini-pumps dispensing morphine, decrease intestinal transit [26].…”

Section: Discussionmentioning

confidence: 99%

“…Opioid receptors have been identified in the small intestine of animals and humans, which when activated lead to decreased peristalsis and increased muscle tone and spasms, resulting in consipation [32, 33]. Both μ and δ opioid receptors have been shown to mediate the delay in GI transit [28]. While morphine has higher affinity for the μ-opioid receptor, it can act on the κ and δ receptors.…”

Section: Discussionmentioning

confidence: 99%

Potentiating effect of morphine on oral Salmonella enterica serovar Typhimurium infection is μ-opioid receptor-dependent

Breslow

Feng

Meissler

et al. 2010

Microbial Pathogenesis

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Previous studies from our laboratory demonstrated that mice treated with morphine pellets are sensitized to Salmonella enterica, serovar Typhimurium infection. However, the opioid receptor antagonist, naltrexone, only partially blocked the effect of morphine, raising the possibility that the opioid might have some of its effects through a nonopioid receptor. To further clarify whether sensitization to infection is an opioid receptor-dependent phenomenon, μ-opioid receptor knock-out (MORKO) mice were used in the present study. Wild type (WT) and MORKO mice were treated with morphine and their sensitivity to oral Salmonella infection assessed by mortality, bacterial burdens in gut associated lymphoid tissue and in blood and peritoneal fluid, and by levels of pro-inflammatory cytokines in plasma. MORKO animals treated with morphine were refractory to a sublethal dose of Salmonella, while similar treatment of WT animals resulted in 100% mortality. WT animals treated with morphine had high bacterial loads in all organs tested, while morphine-treated MORKO animals had no culturable Salmonella in any organs. Pro-inflammatory cytokine levels were elevated in morphine treated WT but not MORKO mice infected with Salmonella. These results provide definitive evidence that the morphine-mediated enhancement of oral Salmonella infection is dependent on the μ-opioid receptor.

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“…Activation of the opioid receptor family has diverse effects on cardiovascular, respiratory and gastrointestinal autonomic functions (Akil et al 1984;Burks et al 1988;Shook et al , 1990Waldhoer et al 2004) with individual responses dependent on the subtype of opioid receptor involved (mu, delta, or kappa) and its location within the CNS. A key site of action is likely to be the nucleus of the tractus solitarius (NTS) in the brain stem, a pivotal integrative center in autonomic regulatory circuits (Spyer 1990).…”

Section: Introductionmentioning

confidence: 99%

Subdivision-Specific Responses of Neurons in the Nucleus of the Tractus Solitarius to Activation of Mu-Opioid Receptors in the Rat

Poole

Deuchars²,

Lewis³

et al. 2007

Journal of Neurophysiology

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Microinjection of opioid receptor agonists into the nucleus tractus solitarius (NTS) has differential effects on cardiovascular, respiratory, and gastrointestinal responses. This can be achieved either by presynaptic modulation of inputs onto neurons or by postsynaptic activation of receptors on neurons in specific regions. Therefore we sought to determine whether responses of neurons to activation of opioid receptors were dependent on their location within the NTS. Using whole cell patch-clamp recordings from neurons within the NTS, the mu opioid receptor (MOR) agonist [D-Ala 2 , N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO, 100 nM) hyperpolarized a proportion of neurons in the medial, dorsomedial and dorsolateral NTS, whereas no postsynaptic responses were observed in remaining subdivisions. DAMGO reduced the amplitude of solitary tract-evoked excitatory postsynaptic potentials (EPSPs) in all neurons tested, regardless of subdivision. The kappa opioid receptor (KOR) agonist U69593 (10 -20 M) also hyperpolarized a small fraction of neurons (6/79) and decreased the amplitude of EPSPs in 50% of neurons. In contrast, the delta-opioid receptor agonist DPDPE (1-4 M) had no presynaptic or postsynaptic effects on NTS neurons even after preincubation with bradykinin. Anatomical data at the light and electron microscopic level complemented electrophysiological observations with respect to MOR location and further showed that MORs were present at both presynaptic and postsynaptic sites in the dorsolateral NTS, often at the same synapse. These data demonstrate site specific responses of neurons to activation of MORs and KORs, which may underlie their ability to modulate different autonomic reflexes.

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II. Regulation of gastrointestinal function by multiple opioid receptors

Cited by 57 publications

References 22 publications

Role of central oxytocin in the inhibition by endotoxin of distension-stimulated gastric acid secretion

Role of central oxytocin in the inhibition by endotoxin of distension-stimulated gastric acid secretion

Potentiating effect of morphine on oral Salmonella enterica serovar Typhimurium infection is μ-opioid receptor-dependent

Subdivision-Specific Responses of Neurons in the Nucleus of the Tractus Solitarius to Activation of Mu-Opioid Receptors in the Rat

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