Biomedical subjects

S Shimohama

Publications and source records attributed to S Shimohama.

165 records · Page 10Linked to original sources

PubMedDate not supplied

Characterization of beta adrenergic receptors in human cerebral arteries and alteration of the receptors after subarachnoid hemorrhage.

The nature of beta adrenergic receptors in human cerebral arteries was characterized and alteration of these receptors after subarachnoid hemorrhage was examined using a radioligand binding assay. The specific 3H-dihydroalprenolol, a beta adrenergic antagonist, binding to human cerebral arteries was saturable and of high affinity (KD = 12.3 nM) with a Bmax of 790 fmol/mg protein. Ki values and Hill coefficients of adrenergic agents for 3H-dihydroalprenolol were as follows; propranolol, 4.1 X 10(-8)M, 1.01; isoproterenol, 1.7 X 10(-6)M, 0.80; epinephrine, 8.3 X 10(-6)M, 0.48; norepinephrine, 2.3 X 10(-5)M, 0.45; metoprolol, 6.8 X 10(-8)M and 7.9 X 10(-6)M, 0.62; butoxamine, 2.2 X 10(-8)M and 2.1 X 10(-6)M, 0.43. The analysis of inhibition of specific 3H-dihydroalprenolol binding by these adrenergic agents suggests that human cerebral arteries contain a high density of beta adrenergic receptors and that the receptors are classified into two types, namely beta 1 and beta 2 adrenergic receptors. The calculated beta 1/beta 2 ratio from Hofstee plots was approximately 4/6. KD and Bmax of 3H-dihydroalprenolol binding to the cerebral arteries after subarachnoid hemorrhage were compared with those of control group. KD and Bmax of 3H-dihydroalprenolol binding of subarachnoid hemorrhage group were 13.9 nM and 1140 fmol/mg protein, respectively. The calculated beta 1/beta 2 ratio was approximately 6/4. These data suggest that the density of total beta adrenergic receptors increased without any significant change in the affinity after subarachnoid hemorrhage and that the increase of beta 1 adrenergic receptors was dominant.

Acebutolol↗

PubMedDate not supplied

Characterization of muscarinic cholinergic receptors in human and dog cerebral arteries.

Various concentrations of acetylcholine (ACh) produced dose dependent relaxations of isolated, helical preparations of human cerebral arteries and these responses were blocked by atropine. The median effective concentration (EC50) of ACh was 6.1 +/- 0.2 X 10(-6)M. ACh produced dual responses in isolated dog cerebral arteries. ACh in low concentrations produced relaxation, and contraction occurred when the concentration was raised to 1 X 10(-5)M. The EC50 of ACh which produced relaxation, in dog cerebral arteries was 7.2 +/- 0.2 X 10(-7)M. Muscarinic cholinergic receptors in these arteries were analyzed directly using 3H-QNB as the ligand. The specific 3H-QNB binding to the arteries was saturable and of KD = 1.5 nM and Bmax = 93 fmol/mg protein in human cerebral arteries and KD = 0.59 nM, Bmax = 340 fmol/mg protein in dog cerebral arteries. Specific binding of 3H-QNB was displaced by muscarinic cholinergic agents. Ki values and Hill coefficients were as follows: QNB, 1.0 X 10(-9)M, 0.89; atropine, 1.1 X 10(-8)M, 0.95; ACh, 0.8 X 10(-8)M and 2.1 X 10(-6)M, 0.54; carbachol, 1.2 X 10(-7)M and 4.3 X 10(-5)M, 0.33 in human cerebral arteries and QNB, 0.55 X 10(-9)M, 0.85; atropine 0.9 X 10(-9)M, 1.00; ACh, 0.9 X 10(-9)M and 1.1 X 10(-6)M, 0.43; carbachol 6.3 X 10(-8)M and 1.1 X 10(-5)M, 0.36 in dog cerebral arteries. Endogenous choline acetyltransferase (ChAT) activity was 1.6 +/- 0.4 nmol/mg protein/hr in human cerebral arteries and 3.7 +/- 0.1 nmol/mg protein/hr in dog cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMedDate not supplied

Differential expression of protein kinase C isozymes in rat cerebellum.

Protein kinase C (PKC) is a family of enzymes found throughout the body, with the greatest diversity and concentration in brain tissue. To understand further the differential role of PKC isozymes in brain, we have raised antibodies against four PKC isoforms--alpha, beta I, beta II and gamma--using specific amino acid sequences predicted from cDNA sequences. On Western blot of rat cerebellar homogenate, these antibodies stained a band of Mr 80,000, a known molecular mass for PKC, except for anti-PKC(beta II), which stained an additional minor Mr 90,000 band. On rat cerebellar sections, specific sets of cells were stained by each antibody. In the molecular layer, stellate and basket cells were stained with anti-PKC(alpha) but not with anti-PKC(beta I), -(beta II), or -(gamma). Anti-PKC (alpha) and anti-PKC(beta II) seemed to stain the Bergmann glial fibre. In the Purkinje cell layer, Purkinje cells were stained with anti-PKC[beta I) and -(gamma). Anti-PKC (alpha) and -(beta II) were negative. Interestingly, a few Purkinje cells were not stained with anti-PKC(gamma). In the granule cell layer, both granule and Golgi cells were stained with anti-PKC(beta I) and -(beta II) but not with anti-PKC(alpha) or -(gamma). Glial cells were stained with anti-PKC(beta II) but not with anti-PKC(alpha), -(beta I), or -(gamma). This study suggests a differential distribution of PKC isoforms in different cells, irrespective of their neurotransmitters. The presence of both positive and negative staining of Purkinje cells with anti-PKC(gamma) raised the possibility of their heterogeneity.

Animals↗