vasoactive-intestinal-peptide and methylatropine

We studied the effects of 14 days' treatment with atropine sulfate (10 or 20 mg/kg per day) or atropine methyl bromide (20 mg/kg per day) on the concentration of vasoactive intestinal polypeptide like-immunoreactivity (VIP-LI) in the rat brain. VIP-LI in the anterior pituitary as well as brain areas dissected from treated and control rats was measured by radioimmunoassay. VIP-LI in the hypothalamus, and especially in the suprachiasmatic nucleus, was not affected by chronic atropine sulfate administration. Conversely, the same treatment induced a decrease in VIP-LI in the cerebral cortex, dorsal raphe, locus coeruleus, ventrolateral and dorsolateral medulla. In these structures, the decrease in VIP-LI was probably due to muscarinic receptor blockade in the central nervous system rather than in the peripheral nervous system since variations in VIP-LI were not observed after atropine methyl bromide treatment. These findings suggest the existence of a muscarinic control of VIP-LI in discrete brain areas of the rat and particularly in caudal brainstem structures.

Topics: Animals; Atropine; Atropine Derivatives; Brain; Male; Muscarinic Antagonists; Radioimmunoassay; Rats; Vasoactive Intestinal Peptide

Helodermin and vasoactive intestinal polypeptide (VIP) are structurally related peptides. We have examined their effects on insulin and glucagon secretion in the mouse. Following intravenous injection, helodermin and VIP equipotently increased plasma glucagon levels with a maximal effect obtained at the dose level of 2 nmol/kg. The maximal response was not augmented by giving the two peptides together at maximal dose levels, showing that helodermin and VIP stimulate glucagon secretion by activating the same mechanisms. Furthermore, both peptides markedly potentiated glucagon secretion stimulated by the cholinergic agonist carbachol, showing that they sensitize glucagon secretion for muscarinic activation. This sensitizing action was abolished by methylatropine, whereas the direct glucagonotropic action of the peptides was insensitive to muscarinic antagonism. Plasma insulin levels were not affected by helodermin but slightly increased by VIP. The study suggests that helodermin and VIP (1) stimulate basal glucagon secretion by the same mechanism, which is insensitive to muscarinic antagonism, (2) sensitize the glucagon secretion for cholinergic activation, and (3) have no or only weak effect on insulin secretion.

Topics: Animals; Atropine Derivatives; Carbachol; Female; Glucagon; Insulin; Insulin Secretion; Intercellular Signaling Peptides and Proteins; Mice; Peptides; Receptors, Muscarinic; Secretory Rate; Stimulation, Chemical; Vasoactive Intestinal Peptide

Recently, gastrin releasing peptide (GRP) was demonstrated to occur within normal thyroidal C cells. In the present study, the effects of GRP on basal and stimulated thyroid hormone secretion were investigated in the mouse according to the McKenzie technique. Iodine-deficient mice were pretreated with 125I and thyroxine. GRP was found dose-dependently to increase the basal radioiodine levels after iv injection, reflecting a stimulation of basal thyroid hormone secretion. The effect was maximal at a dose level of 3.0 nmol/animal, and at 2 h after injection, when GRP had increased blood radioiodine levels to 152 +/- 8% compared with 96 +/- 5% in controls (P less than 0.001). GRP seemed to exert additive effects on thyroid hormone secretion with vasoactive intestinal peptide and with TSH at a threshold dose level. In contrast, GRP did not influence the stimulatory effects of either a half-maximal dose level of TSH or noradrenaline. Furthermore, neither L-propranolol nor methylatropine influenced the GRP-induced thyroid hormone secretion. It is concluded that GRP has the capacity to stimulate basal thyroid hormone secretion in the mouse.

Topics: Animals; Atropine Derivatives; Dose-Response Relationship, Drug; Female; Gastrin-Releasing Peptide; Mice; Mice, Inbred Strains; Norepinephrine; Peptides; Propranolol; Thyroid Hormones; Thyrotropin; Vasoactive Intestinal Peptide

Acetylcholine (ACh) and vasoactive intestinal peptide (VIP) probably coexist in cholinergic neurons of rodent salivary glands. In this tissue, cholinergic drugs regulate release of both ACh and VIP from postganglionic cholinergic neurons. In the present study we investigated whether VIP could modulate the metabolism of ACh in mouse submandibular gland cholinergic neurons using ACh turnover rate (TRACh) as a parameter. The TRACh was estimated via measurement of the formation of [3H]ACh during constant rate infusion of [3H]choline. Choline and ACh were separated by reverse phase high-performance liquid chromatography and were detected electrochemically after enzymatic postcolumn reaction. We calculated that the TRACh was about 3 nmol/mg of protein per hr. Pilocarpine, a muscarinic agonist decreased the TRACh about 5-fold whereas atropine methyl Br, a muscarinic antagonist, caused a large increase in turnover. Turnover, therefore, appears to be regulated by a feedback mechanism triggered by occupancy of postsynaptic receptors. VIP infused i.v. (40 micrograms/kg/min) decreased the TRACh by about 50%. Atropine completely prevented the inhibition of the TRACh induced by VIP. These results suggest that, by changing postsynaptic or presynaptic muscarinic receptor function, VIP may participate in the control of ACh metabolism. Parasympathetic decentralization of salivary glands did not prevent the effect of either atropine or VIP on TRACh. This finding suggests that the central afferent input to the ganglionic cells is not required for the regulation of ACh metabolism and, therefore, the feedback loop probably acts via a postganglionic mechanism which is not elucidated by present experiments.

Topics: Acetylcholine; Animals; Atropine; Atropine Derivatives; Choline; Chromatography, High Pressure Liquid; Male; Metabolic Clearance Rate; Mice; Neurons; Parasympathetic Nervous System; Pilocarpine; Salivary Glands; Submandibular Gland; Vasoactive Intestinal Peptide