Enhancement of [m-methoxy 3H]MDL100907 binding to 5HT 2A receptors in cerebral cortex and brain stem of streptozotocin induced diabetic rats

5-Hydroxytryptamine2A (5-HT2A) receptor kinetics was studied in cerebral cortex and brain stem of streptozotocin (STZ) induced diabetic rats. Scatchard analysis with [3H] (±) 2,3dimethoxyphenyl-l-[2-(4-piperidine)-methanol] ([3H]MDL100907) in cerebral cortex showed no significant change in maximal binding (Bmax) in diabetic rats compared to controls. Dissociation constant (K) of diabetic rats showed a significant decrease (p < 0.05) in cerebral cortex, which was reversed to normal by insulin treatment. Competition studies of [3H]MDL100907 binding in cerebral cortex with ketanserin showed the appearance of an additional low affinity site for 5-HT2A receptors in diabetic state, which was reversed to control pattern by insulin treatment. In brain stem, scatchard analysis showed a significant increase (p < 0.05) in Bmax accompanied by a significant increase (p < 0.05) in Kd. Competition analysis in brain stem also showed a shift in affinity towards a low affinity State for 5-HT2A receptors. All these parameters were reversed to control level by insulin treatment. These results show that in cerebral cortex there is an increase in affinity of 5-HT2A receptors without any change in its number and in the case of brain stem there is an increase in number of 5HT2A receptors accompanied by a decrease in its affinity during diabetes. Thus, from the results we suggest that the increase in affinity of 5-HT2A receptors in cerebral cortex and upregulation of 5-HT2A receptors in brain stem may lead to altered neuronal function in diabetes.

Serotonin Receptor Gene Expression And Insulin Function In Streptozotocin Induced Diabetic Rats

Recent studies have established a fimctional correlation of serotonergic and adrenergic function in the brain regions with insulin secretion in diabetic rats (Vahabzadeh et al., 1995). Administration of 5-HT”. agonist 8-OH-DPAT to conscious rats caused an increase in blood glucose level. This increase in blood glucose is due to inhibition of insulin secretion by increased circulating EPI (Chaouloff et al., 1990a; Chaouloff et al., 1990d; Chaoulo1T& Jeanrenaud, 1987). The increase in EPI is brought about by increased sympathetic stimulation. This increase can lead to increased sympatho-medullary stimulation thereby inhibiting insulin release (Bauhelal & Mir, 1993, Bauhelal & Mir, 1990a; Chaouloffet al., 1990d). Also, studies have shown that Gi protein in the liver has been decreased in diabetes which will increase gluconeogenesis and glycogenolysis thereby causing hyperglycaemia (Pennington, 1987). Serotonergic control is suggested to exert different effects on insulin secretion according to the activation of different receptor subclasses (Pontiroli et al., 1975). In addition to this mechanism, the secretion of insulin is dependent on the turnover ratio of endogenous 5-hydroxy tryptophan (5-HTP) to 5-HT in the pancreatic islets (Jance er al., 1980). The reports so far stated does not explain the complete mechanism and the subclass of 5-HT receptors whose expression regulate insulin secretion in a diabetic state. Also, there is no report of a direct regulation of insulin secretion by 5-HT from the pancreatic islets even though there are reports stating that the pancreatic islets is a rich source of 5-HT (Bird et al., 1980). Therefore, in the present study the mechanism by which 5-HT and its receptors regulate insulin secretion from pancreatic [3-cells was investigated. Our results led to the following hypotheses by which 5-HT and its receptors regulate the insulin secretion.

Portraits of Whistler : a critical study and an iconography /

"Two hundred and fifty copies printed during November, 1918, by D.B. Updike, the Merrymount Press, Boston, USA. The first twenty-five copies printed have been numbered and signed by the author ..."--Colophon.

Whistler's pastels and other modern profiles,

Reprinted in part from Art and progress and the International studio.

The dier's assistant in the art of dying wool and woollen goods : extracted from the philosophical and chymical works of those most eminent authors Ferguson, Dufay, Hellot, Geoffery, Colbert; and that reputable French dier, Mons. de Julienne : translated from the French : with additions and practical experiments /

First published in Leeds, 1778.

The thinking bayonet /

Menendez. Civil War novels,

Tobacco, and its effect upon health and character of those who use it /

Mode of access: Internet.

Whistler v. Ruskin : art & art critics /

Printed brown paper cover dated Dec. 24, 1878.

Outcome of the civil war, 1863-1865,

"Critical essay on authorities": p. [307]-327.

An account of the Pelew Islands, situated in the western part of the Pacific Ocean : composed from the journals and communications of Captain Henry Wilson and some of his officers who, in August 1783, were there shipwrecked, in the Antelope ... /

A vocabulary of the pelew language: p. 365-378.

Letters to a young physician just entering upon practice /

Mode of access: Internet.

Armenia and the Armenians : being a sketch of its geography, history and church /

Includes bibliographical references (p. 8)

History of the French Revolution, and of the wars resulting from that memorable event.

Mode of access: Internet.

A history of the western division of the county of Sussex.

Mode of access: Internet.

Whistler,

Mode of access: Internet.