Disease relevance of RX 77368

• Fos-immunoreactive cells were rare in controls (~1 cell/ganglion), whereas intracisternal RX-77368 (50 ng) increased the number to 24.8 +/- 1.8 and 26.8 +/- 2.2 cells/ganglion in the corpus and antrum, respectively [1].
• Measurements of core temperature and respiration rate in rats following intra-accumbens or septal injection of TRH, CG 3509 and RX 77368 showed these peptides to reverse pentobarbitone-induced hypothermia and stimulate respiration rate [2].
• In urethane-anesthetized, gastric fistula rats, intracisternal RX 77368 or TRH induced stimulation of gastric acid output which was rapid in onset, long lasting, and dose-dependent, in doses ranging from 3 to 100 ng/rat for RX 77368, and 0.1 to 1 micrograms/rat for TRH [3].
• These findings indicate that [4Cl-D-Phe6,Leu17]VIP is an antagonist for exogenous VIP-induced gastric hyperemia and hypotension and that VIP modulates the systemic blood pressure response to IC RX 77368 at 30 ng while not playing a primary role in the increase of GMBF [4].
• Of particular interest was the finding that RX-77368 not only blocked the effects of NT but also produced hyperalgesia [5].

Psychiatry related information on RX 77368

• RX 77368-induced enhancements of gastric defense mechanisms did not occur as a result of acid secretion [6].

High impact information on RX 77368

• Omeprazole abolished RX 77368-induced acid secretion but did not alter its effects on gastric defense mechanisms [6].
• Gastric acid output measured in conscious rats 2 hours after pylorus ligation was not modified by intracisternal injection of RX 77368 at 1.5 ng but was significantly increased by 54% at the 3-ng dose [7].
• IC injection of interleukin-1 beta inhibited vagally stimulated gastric acid secretion induced by IC injection of the stable thyrotropin-releasing hormone analogue RX 77368 [8].
• Medullary sites of action of the TRH analogue, RX 77368, for stimulation of gastric acid secretion in the rat [9].
• Intrathecal injection of RX 77368 at doses up to 2500 pmol did not modify gastric acid secretion [9].

Chemical compound and disease context of RX 77368

• The role of gastrin, acetylcholine and histamine in the acid response to central vagal activation induced by intracisternal injection of the stable analog, RX 77368, was further investigated in urethane-anesthetized rats with gastric fistula [10].
• The stimulation of gastric acid and serotonin release occurred 15 and 30 min, respectively, after intracisternal injection of RX 77368 (100 ng) and lasted for over 2 h, as measured in urethan-anesthetized rats with gastric fistula [11].

Biological context of RX 77368

• 3. RX-77368 (1.5, 3, 10, 30 and 100 ng, i.c.) dose-dependently increased corpus contractions, expressed as total area under the curve (AUC, mV min(-1)) to 2.6+/-2.5, 6.1+/-5.9, 9.8+/-2.6, 69.7+/-21.7 and 74.9+/-28.7 respectively vs 0.2+/-0.1 after i.c. saline [12].
• The VIP antagonist did not significantly reduce the GMBF response to IC RX 77368 while enhancing the rise in blood pressure [4].
• L-NG-Nitro-arginine methyl ester (L-NAME, 3 mg/kg i.v.), an inhibitor of NO synthase, abolished the cytoprotection provided by i.c. RX 77368 [13].
• The stable analog, RX 77368, unlike TRH, stimulated gastric emptying when the meal was given 60 min after peptide injection [14].
• These results demonstrate that chemical stimulation of the raphe pallidus and obscurus by RX 77368 stimulates gastric contractility through vagal and muscarinic pathways [15].

Anatomical context of RX 77368

• The effects of RX 77368 and potassium alone (15 mM) on NA release from both spinal cord and brainstem slices were reduced to basal levels with tetrodotoxin (10(-7) M) [16].
• In contrast TRH and its analogs, RX 77368 and DN-1417, were approximately 2 to 8 times more active in striatum than amygdala membranes [17].
• These results indicated that central vagal efferent stimulation by intracisternal RX-77368 activates gastric myenteric neurons as well as glial cells mainly through nicotinic ACh receptors in conscious rats [1].
• In rats, the increase in gastric mucosal blood flow evoked by a low ic dose of RX 77368 occurs via release of calcitonin gene-related peptide from capsaicin-sensitive afferent neurons, most probably of spinal origin [18].
• To assess early changes in the gastric mucosa after intracisternal injection of a stable TRH analog, pGlu-His-(3,3'-dimethyl)-ProNH2 (RX-77368), we measured the blood-to-lumen 51Cr-labeled EDTA clearance and examined the effects of vagotomy, atropine, omeprazole, and hydrochloric acid (HCl) on RX-77368-induced mucosal permeability [19].

Associations of RX 77368 with other chemical compounds

• Hepatic DNA synthesis was assessed by [Methyl-3H]thymidine incorporation 6, 12, 24, 48, and 72 hours after intracisternal injection of the TRH analog, RX 77368 (1, 5, 10, and 100 ng), and by 5-bromo-2'-deoxyuridine (BrdU) labeling of the liver section [20].
• Intracisternal injection (ic) of the stable TRH analog RX 77368 (10 ng) induced significantly higher insulin response in both genders of overnight-fasted GK rats compared with Wistar rats and slightly increased blood glucose in female Wistar rats but significantly decreased it from 193 to 145 mg/100 ml in female GK rats [21].
• Activation of gastric myenteric cells by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368, at a dose inducing near maximal vagal cholinergic stimulation of gastric functions, was investigated in conscious rats [1].
• These data show that i.c. CRF injection acts centrally to inhibit gastric contractions stimulated centrally (i.e. by i.c. RX 77368) but not peripherally (i.e. by carbachol), and by inference reduces the risk of erosion formation induced by some stressors [22].
• Dose-response studies revealed that the gastric acid secretion induced by submaximal but not high doses of RX 77368 was elevated significantly by p-CPA pretreatment. p-CPA also enhanced the gastric acid output produced by submaximal, but not high doses of the vagal stimulant baclofen, [beta-(p-chlorophenyl)-gamma-aminobutyric acid] [23].

Gene context of RX 77368

• Contractility was stimulated by intravenous carbachol (100 mg/kg/h) or i.c. injection of the TRH analog, RX 77368 [22].
• Intravenous CRF was 1/10th as potent in suppressing contractions produced by i.c. RX 77368 [22].
• Ucn (1, 3 or 10 microg) inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93% respectively vs i.c. saline+RX-77368 [12].
• Intracisternal injection of TRH or its potent analog RX 77368 appears also as a new, simple method to produce centrally mediated experimental gastric erosions in 24 hr-fasted rats [24].
• Ucn II (3, 10, and 30 microg/kg, i.v.) did not alter the 20 min net rise in MAP induced by RX-77368 (35.7+/-7.1, 32.6+/-3.3 and 24.6+/-6.9 mm Hg, respectively) compared with vehicle (33.6+/-4.3 mm Hg) [25].

Analytical, diagnostic and therapeutic context of RX 77368

• The gastric secretory response to microinjection of RX 77368 into the nucleus ambiguus was dose related (0.7-77 pmol), long-lasting (greater than 90 min), and blocked by vagotomy [9].
• The stimulation of hepatic blood flow by RX-77368 microinjection into the left DVC was eliminated by left cervical and hepatic branch vagotomy but not by right cervical vagotomy [26].
• After measuring basal flow, a stable TRH analogue (RX-77368) was microinjected into the DVC and hepatic blood flow response was observed for 120 minutes by laser Doppler flowmetry [26].
• Bilateral vagotomy blocked ic RX 77368-induced insulin secretion, whereas adrenalectomy abolished its hyperglycemic effect [21].
• Intragastric perfusion with HCl did not change the RX-77368 (15 ng)-induced increase in permeability, but completely inhibited the recovery of permeability after the peak [19].

References