Tohru Nakajima

Quantitative autoradiographic localization of neuropeptide Y receptors in the rat lower brainstem

Using quantitative autoradiography, we have characterized the binding of 125I-Bolton-Hunter coupled neuropeptide Y ([125I]NPY) and observed the localization of 125I-NPY receptors in the rat lower brainstem. [125I]NPY bound to the receptors in a specific, saturable and reversible manner with high affinity. The binding was blocked only by unlabeled NPY but not by NPY-related peptides i.e. peptide YY, pancreatic polypeptide (avian and human), nor by neurotensin. [125I]NPY receptors were revealed to be coupled to the guanosine triphosphate (GTP)-binding protein. Regional distribution study showed that [125I]NPY has a distinctive pattern of distribution in the rat lower brainstem, being particularly concentrated in the area postrema and the medial subnucleus of the nucleus tractus solitarii. These results suggest that such NPY receptors have an important role in cardiovascular regulation.

Higher density of 125I-neuropeptide Y receptors in the area postrema of SHR

125I-Neuropeptide Y (125I-NPY) binding capacities were quantitated in the areas postrema of young (5 weeks) and adult (20 week SHR and compared with age-matched WKY rats using autoradiography. The maximum binding capacity (Bmax) was significantly higher in the area postrema of adult SHR, while no difference was seen at the age of 5 weeks. Our result supports the idea of a functional role for NPY receptors in the central control of blood pressure. NPY receptors in the area postrema may be involved in the perception of circulating NPY resulting in the alteration of the neuronal activity of the nucleus tractus solitarii.

Elevation of adenosine 3',5'-monophosphate in the perfusate of rat kidney after addition of dopamine.

Dopamine (10-4 M) and vasopressin (1 mU/ml) were found to increase the level of cyclic AMP in the perfusate of rat kidney. There were some differences in the mode of action of these two drugs. Firstly, the effect of dopamine, but not of vasopressin, was completely antagonized by spiroperidol. Secondly, the maximal response was attained within 1 min after dopamine perfusion, but 8 min after vasopressin perfusion. These results suggest that a specific dopamine receptor which acts to increase the concentration of cyclic AMP is located in the vascular tissue of rat kidney.

Y-26763 protects the working rat myocardium from ischemia/reperfusion injury through opening of KATP channels

This investigation was undertaken to determine the possible protection against ischemia afforded by Y-26763, [(-)-(3S,4R)-4-(N- acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran- 3- ol], which has K+ channel-opening properties, in isolated rat hearts under working conditions. This preparation was subjected to 28 min of global ischemia followed by 30 min of reperfusion. Drugs were injected into the aortic cannula prior to ischemia. Compared to control, Y-26763 (1 microM) resulted in a significant recovery of post-ischemic cardiac functions, significant reduction of cellular enzyme loss, and preserved significantly the stocks of cellular high-energy phosphates and the myocyte ultrastructure. These effects of Y-26763 were completely prevented by glibenclamide (10 microM), a specific K+ channel blocker of KATP channels. In non-ischemic conditions, Y-26763 significantly increased coronary flow without affecting cardiac output and heart rate. The data were analyzed statistically by analysis of variance. The results clearly demonstrate that Y-26763 protects the myocardium from ischemic injury by opening KATP channels.