Effect of central administration of motilin on migrating complexes in the dog

1987 ◽  
Vol 252 (2) ◽  
pp. G195-G199 ◽  
Author(s):  
M. Hashmonai ◽  
V. L. Go ◽  
T. Yaksh ◽  
J. H. Szurszewski

The effects of intravenous, intrathecal, and intracerebroventricular injection of motilin on the interdigestive myoelectric (MMC) activity of the stomach and small intestine were examined in conscious dogs. To monitor electrical activity, electrodes were implanted on the stomach and small bowel. To inject motilin into the central nervous system, catheters were chronically positioned in the intrathecal space at the lumbar level and in one of the lateral cerebral ventricles. In all dogs, intravenous injection of motilin caused a transient increase in the plasma concentration of motilin and initiated gastric MMCs, which propagated aborally to the ileum. Intrathecal and intracerebroventricular injections of motilin did not affect plasma motilin levels and did not induce MMCs. These data suggest that initiation of MMCs after intravenous injections of motilin occurs through receptors for motilin possibly located outside the central nervous system. These data also suggest the hypothesis that initiation of naturally occurring MMCs in the dog may not be dependent on endogenous release of motilin from the central nervous system.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi Wen ◽  
Nazila Salamat-Miller ◽  
Keethkumar Jain ◽  
Katherine Taylor

AbstractDirect delivery of therapeutic enzymes to the Central Nervous System requires stringent formulation design. Not only should the formulation design consider the delicate balance of existing ions, proteins, and osmolality in the cerebrospinal fluid, it must also provide long term efficacy and stability for the enzyme. One fundamental approach to this predicament is designing formulations with no buffering species. In this study, we report a high concentration, saline-based formulation for a human sulfatase for its delivery into the intrathecal space. A high concentration formulation (≤ 40 mg/mL) was developed through a series of systematic studies that demonstrated the feasibility of a self-buffered formulation for this molecule. The self-buffering capacity phenomenon was found to be a product of both the protein itself and potentially the residual phosphates associated with the protein. To date, the self-buffered formulation for this molecule has been stable for up to 4 years when stored at 5 ± 3 °C, with no changes either in the pH values or other quality attributes of the molecule. The high concentration self-buffered protein formulation was also observed to be stable when exposed to multiple freeze–thaw cycles and was robust during in-use and agitation studies.


1997 ◽  
Vol 272 (5) ◽  
pp. H2361-H2368 ◽  
Author(s):  
R. L. Davisson ◽  
M. D. Travis ◽  
J. N. Bates ◽  
A. K. Johnson ◽  
S. J. Lewis

This study examined whether the stereoselective actions of S-nitrosocysteine (SNC) in the central nervous system involves the activation of stereoselective SNC recognition sites. We examined the effects produced by intracerebroventricular injection of the L- and D-isomers of SNC (L- and D-SNC) on mean arterial blood pressure, heart rate, and vascular resistances in conscious rats. We also examined the hemodynamic effects produced by intracerebroventricular injections of 1) L-cystine, the major non-nitric oxide (NO) decomposition product of L-SNC, 2) the parent thiols L- and D-cysteine, and 3) the bulky S-nitrosothiol L-S-nitroso-gamma-glutamylcysteinylglycine [L-S-nitrosoglutathione, (L-SNOG)]. Finally, we examined the decomposition of L- and D-SNC and L-SNOG to NO on their addition to brain homogenates. The intracerebroventricular injection of L-SNC (250-1,000 nmol) produced falls in mean arterial pressure, increases in heart rate, and a dose-dependent pattern of changes in hindquarter, renal, and mesenteric vascular resistances. The intracerebroventricular injections of D-SNC, L-cystine, and L-SNOG produced only minor effects. The intracerebroventricular injection of L-cysteine produced pressor responses and tachycardia, whereas D-cysteine was inactive. L- and D-SNC decomposed equally to NO on addition to brain homogenates. L-SNOG decomposed to similar amounts of NO as L- and D-SNC. These results suggest that SNC may activate stereoselective SNC recognition sites on brain neurons and that S-nitrosothiols of substantially different structure do not stimulate these sites. These recognition sites may be stereoselective membrane-bound receptors for which L-SNC is the unique ligand.


2001 ◽  
Vol 2 (3) ◽  
pp. 201-209 ◽  
Author(s):  
Takeshi Nonomura ◽  
Atsushi Tsuchida ◽  
Michiko Ono-Kishino ◽  
Tsutomu Nakagawa ◽  
Mutsuo Taiji ◽  
...  

It has been previously demonstrated that brain-derived neurotrophic factor (BDNF) regulates glucose metabolism and energy expenditure in rodent diabetic models such as C57BL/KsJ-leprdb/leprdb(db/db) mice. Central administration of BDNF has been found to reduce blood glucose indb/dbmice, suggesting that BDNF acts through the central nervous system. In the present study we have expanded these investigations to explore the effect of central administration of BDNF on energy metabolism. Intracerebroventricular administration of BDNF lowered blood glucose and increased pancreatic insulin content ofdb/dbmice compared with vehicle-treated pellet pair-feddb/dbmice. While body temperatures of the pellet pair-feddb/dbmice given vehicle were reduced because of restricted food supply in this pair-feeding condition, BDNF treatment remarkably alleviated the reduction of body temperature suggesting the enhancement of thermogenesis. BDNF enhanced norepinephrine turnover and increased uncoupling protein-1 mRNA expression in the interscapular brown adipose tissue. Our evidence indicates that BDNF activates the sympathetic nervous systemviathe central nervous system and regulates energy expenditure in obese diabetic animals.


1991 ◽  
Vol 555 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Carla Gambarana ◽  
Gregory A. Ordway ◽  
Miroslawa Hauptmann ◽  
Shanaz Tejani-Butt ◽  
Alan Frazer

1995 ◽  
Vol 73 (7) ◽  
pp. 1042-1046 ◽  
Author(s):  
J. F. Flood ◽  
S. A. Farr ◽  
H. J. Perry III ◽  
F. E. Kaiser ◽  
P. M. K. Morley ◽  
...  

Amylin has been demonstrated to decrease food intake in mice and rats. Amylin is effective when delivered both peripherally and directly into the central nervous system. Amylin's effect on food intake is not aversive. Amylin may produce its effect on food intake by modulating nitric oxide synthesis. Calcitonin gene related peptide also decreases food intake after peripheral and central administration. In addition, amylin has been demonstrated to modulate memory at both peripheral and central sites.Key words: appetite, retention, satiety, memory, amylin.


2021 ◽  
Vol 32 (4) ◽  
pp. 303-306
Author(s):  
A. I. Smirnov ◽  
G. M. Shpuga

The effect of morphine on the organism of animals is one of the important problems of pharmacology, since with subcutaneous and intravenous injections, it acts differently on different animals, and its effect on the central nervous system is manifested in vice anesthesia or excitation.


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