piperidines and slaframine

The influence of slaframine (SF), a parasympathomimetic compound isolated from the fungus Rizoctonia leguminicola, on circulating metabolic hormone concentrations was investigated in goats. In Exp. 1, SF was administered i.v. at 0 (CONT), 50 (LSF), 100 (MSF), or 150 (HSF) microgram/kg.75 BW in four mature Spanish-cross does (average BW 36 +/- 7 kg) fitted with indwelling jugular vein catheters in a 4 x 4 Latin square design. Plasma glucose peaked (P < .06) at 120 min with LSF and at 180 min with HSF and was higher (P <.06) than the CONT at these times. Glucose exhibited a quadratic response (P < .03) to SF. Area under the response curve for glucose differed (P < .02) in HSF from CONT and MSF. Insulin peaked (P < .01) at 240 min with MSF and at 180 min with HSF. Plasma triiodothyronine was maintained at a higher level (P < .03) with HSF. Thyroxine peaked (P < .06) at 120 min with MSF and 300 min with HSF. Plasma NEFA and somatotropin concentrations were not affected (P > .10) by SF. In Exp. 2, four mature Spanish-cross wethers (average BW 27 +/- 2 kg) fitted with jugular vein catheters were administered SF (0 and 114 micrograms/kg.75 BW) and 4-diphenylacetoxy-N-methylpiperidine methiodide (4DAMP; 0 and 258 micrograms/kg.75 BW), a M3-muscarinic receptor antagonist, i.v. in a 4 x 4 Latin square design with a 2 x 2 factorial arrangement of treatments. With SF, glucose peaked (P < .06) at 60 min and insulin peaked (P < .05) at 180 min. Plasma triiodothyronine levels were maintained (P < .05) with SF but declined with other treatments. Plasma NEFA and thyroxine concentrations remained unchanged regardless of treatment. Slaframine administration induced hyperglycemia and hyperinsulinemia in goats; however, these changes were blocked by preadministration of isomolar quantities of the M3-muscarinic receptor antagonist, 4DAMP.

Topics: Alkaloids; Animals; Blood Glucose; Endocrine Glands; Fatty Acids, Nonesterified; Female; Goat Diseases; Goats; Growth Hormone; Hyperglycemia; Hyperinsulinism; Injections, Intravenous; Insulin; Male; Muscarinic Agonists; Muscarinic Antagonists; Parasympathomimetics; Piperidines; Receptors, Muscarinic; Thyroxine; Triiodothyronine

Three Holstein steers (345 +/- 22 kg) surgically fitted with a pancreatic cannula were used in two 3 x 3 Latin square design experiments to examine the effects of slaframine (SF), a muscarinic agonist, or 4-diphenylacetoxy-N-methylpiperidine methiodide (4DAMP), an M3 muscarinic glandular receptor antagonist, on pancreatic exocrine secretion. Pancreatic exocrine secretion was collected for 8 h postdosing at 30-min intervals beginning 1 h postfeeding. In experiment 1, steers were dosed with 0, 25, or 50 micrograms.kg-1 body weight (BW) of SF. Secretion of pancreatic juice and the pH of the secreted juice increased linearly (p < 0.05) with SF; however, secretion rate showed a time by treatment interaction (p < 0.05), as treatments converged 7 h postdosing. Trypsin secretion tended (p < 0.10) to show a quadratic response to SF administration, with the 25 micrograms SF.kg-1 BW dose having the lowest value. In experiment 2, steers received 50 micrograms.kg-1 BW of SF (positive control), 113 micrograms.kg-1 BW of 4DAMP (isosmolar with SF), or both. SF caused a greater pancreatic fluid secretion (p < 0.10) than 4DAMP, with SF plus 4DAMP intermediate. A time by treatment interaction (p < 0.04) was found, since treatments converged 8 h postdosing. Trypsin secretion was higher (p < 0.05) for SF than the other treatments. Chymotrypsin, alpha-amylase, and protein secretion were not affected. SF and 4DAMP alter pancreatic fluid secretion in the steer but have minimal effects on enzyme secretions.

Topics: Alkaloids; alpha-Amylases; Animals; Cattle; Chymotrypsin; Hydrogen-Ion Concentration; Male; Muscarinic Antagonists; Pancreas; Pancreatic Juice; Parasympatholytics; Parasympathomimetics; Piperidines; Proteins