title: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine.
abstract: 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.
authors.affiliation: Department of Animal Science, Louisiana State University Agricultural Center, Baton Rouge 70803-4210, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Chapa
authors.forename: J M
authors.initials: JM
authors.lastname: Fernandez
authors.forename: D L
authors.initials: DL
authors.lastname: Thompson
authors.forename: R J
authors.initials: RJ
authors.lastname: Tempelman
authors.forename: L F
authors.initials: LF
authors.lastname: Berrio
authors.forename: W J
authors.initials: WJ
authors.lastname: Croom
authors.forename: W M
authors.initials: WM
authors.lastname: Hagler
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004702:Endocrine Glands / Q000187:drug effects / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015511:Goat Diseases / Q000097:blood / Q000139:chemically induced; D006041:Goats / Q000097:blood / Q000502:physiology*; D013006:Growth Hormone / Q000097:blood; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced / Q000662:veterinary; D006946:Hyperinsulinism / Q000097:blood / Q000139:chemically induced / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007328:Insulin / Q000097:blood; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D000470:Alkaloids; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010277:Parasympathomimetics; D010880:Piperidines; D011976:Receptors, Muscarinic; D014284:Triiodothyronine; C009275:slaframine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D013006:Growth Hormone; D013974:Thyroxine