Various hypothalamic lesions were placed in long term ovariectomized rats, and their effects on pulsatile discharges of LH were noted in order to determine which neural regions are involved in the control of this mode of LH secretion. Complete hypothalamic deafferentiation did not affect pulsatile patterns of LH secretion unless the anterior portion of the cut also lesioned the anterior portion of the arcuate nuclei, in which case pulsatile LH discharges were completely blocked. Pulsatile LH secretion was not blocked by bilateral electrolytic lesions placed in ventromedial, paraventricular, or suprachiasmatic nuclei or anterior or posterior portions of the arcuate nuclei, although the nuclei were not completely destroyed by the lesions. When bilateral electrolytic lesions of the anterior portions of the arcuate nuclei were combined with anterior hypothalamic deafferentation, however, pulsatile discharges of LH were completely blocked. These results suggest that two pathways can stimulate the pulsatile mode of LH secretion independently of each other. One of these pathways involves the arcuate nuclei and possibly nearby structures, while the other appears to include extrahypothalamic structures and to enter the hypothalamus anteriorly.

The present study determined the effects of nitric oxide (NO) synthase induction on ethanol-mediated damage to rat gastric mucosa. NO synthase activity was determined by [14C]arginine conversion to radiolabeled citrulline. Ca(2+)-independent NO synthase activity was determined by citrulline formation in the presence of EGTA (1 mM) in the incubation mixture. Intraluminal ethanol administration (2 mL; 40% w/v) to control rats resulted in an increase in mucosal damage characterized as vasocongestion and hemorrhagic necrosis and a reduction in Ca(2+)-dependent NO synthase activity. Administration of Escherichia coli lipopolysaccharide (LPS; 3 mg/kg i.v.) augmented Ca(2+)-independent NO synthase activity (determined 4 h later) and reduced damage in response to intraluminal ethanol instillation. Ethanol treatment did not significantly affect induction of NO synthase activity. Dexamethasone pretreatment (1 mg/kg i.v. 2 h before LPS administration) reduced both Ca(2+)-independent NO synthase activity and the gastroprotective effect of LPS against ethanol-mediated mucosal injury. Likewise, concurrent administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg s.c.) inhibited the gastroprotection associated with LPS treatment, an effect abolished by pretreatment with the NO substrate L-arginine (300 mg/kg s.c.). Indomethacin (5 mg/kg i.v.) was ineffective in suppressing LPS-mediated gastroprotection. These results suggest that while Ca(2+)-dependent NO formation is inhibited by ethanol treatment, the inducible Ca(2+)-independent NO synthase plays a role in LPS-mediated gastroprotection against ethanol-mediated damage to the gastric mucosa.

SUMMARY1. We have examined gastrointestinal mucosal growth 30 days after surgical removal of the submandibular-sublingual salivary glands and ligation of the parotid ducts of rats. The rate of [3H]thymidine uptake in vitro as an estimation of DNA synthesis and the content of DNA and RNA were examined in the oxyntic, duodenal and proximal colonic mucosa.2. DNA synthesis, DNA and RNA content of oxyntic mucosa were reduced in sialoadenectomized rats when compared to sham-sialoadenectomized control animals. There was no change in the degree of [3H]thymidine incorporation or DNA content of the duodenal or colonic mucosa.3. Intraperitoneal injection ofan aqueous extract ofthe submandibular-sublingual salivary glands of rats (4-0 mg tissue protein in 0-1 M-sodium phosphate buffer administered twice a day for 15 days) increased the rate of DNA synthesis and the total mucosal DNA and RNA content in the oxyntic mucosa. Injections of extracts of spleen or muscle did not produce consistent results.4. Administration of epidermal growth factor (10 jug/kg) or pentagastrin (250 psg/kg) resulted in an increase of the level of DNA synthesis observed in the oxyntic mucosa of sialoadenectomized rats. 5. Plasma and antral tissue levels of the trophic hormone, gastrin, were not significantly decreased in sialoadenectomized rats treated with 041 M-sodium phosphate-buffered saline. However, treatment with the salivary tissue extract did result in significant reductions in both plasma and tissue levels of gastrin.6. We conclude that elimination of the major salivary glands in the rat results in a decrease in [3H]thymidine uptake and DNA content of the gastric oxyntic mucosa. These effects are not mediated via a reduction in endogenous levels of the trophic hormone, gastrin. Administration of an aqueous extract of salivary tissue exerted a small but significant trophic influence on the oxyntic mucosa of the rat.

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Biologically active [3H]prostaglandin E2 (PGE2) bound rapidly and specifically to membrane fractions from hog fundic mucosa. Optimal binding occurred in the 30,000-g membrane preparation at 37 degrees C (pH 5.0). Scatchard analysis of specific PgE2 binding revealed the presence of a heterogeneous population of binding sites with Kd values and binding site concentrations of approximately 1 X 10(-9) M and 1 fmol/mg prot and 2 X 10(-8) M and 20 fmol/mg prot, respectively. Specific binding was inhibited by the following agents in descending order of potency: PGE1, PGA2, PGD2, 6-keto-PGF1 alpha, and thromboxane B2. Trypsin treatment or boiling reduced or abolished specific PGE2 binding. PGE2 stimulated cAMP formation in the 2,500-g fraction, with an approximate Km of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not be localized in these fractions in vitro.