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Fura 2 loaded thoracic aorta strips from rabbits were used. Norepinephrine, phenylephrine, clonidine, and tizanidine induced an increase in cytosolic Ca2+ concentration [( Ca2+]i) and muscle tension in a concentration-dependent manner. A positive correlation between [Ca2+]i and tension development owing to the agonists was noted. The slope of regression lines between [Ca2+]i and tension development for clonidine and tizanidine, alpha 1-adrenergic partial agonists, were significantly steeper than those for norepinephrine and phenylphrine, alpha 1-adrenergic full agonists. The intrinsic activities of the partial agonists obtained from tension development were greater than those from changes in [Ca2+]i. These results suggest that the partial agonists cause a greater muscle tension than the full agonists at the same level of [Ca2+]i.

Sensitivity (pD2 value, negative logarithm of the molar concentration producing the half maximum response) and affinity (pKA value, negative logarithm of dissociation constant) of norepinephrine were determined in 6 arteries from rabbits. A positive correlation was found in the pD2 and pKA values of norepinephrine. The slope was not significantly different from 1. The pD2 and pKP (a negative logarithm of dissociation constant of a partial agonist) values of tizanidine, an a,-partial agonist, were also determined. There were positive correlations between the pD2 and pKP values of tizanidine and also between the two pD2 values of norepinephrine and tiza nidine. The slopes were not significantly different from 1. These results suggest that the regional differences in pD2 values of norepinephrine and tizanidine in the arteries are partly due to the affinity and suggest that both drugs interact with one recognition site in the al-adrenoceptors. The dissociation constants, KD values, and the maximum binding sites, Bmax, for [125I]-HEAT were also estimated by Scatchard analysis of the specific binding of [125I]-HEAT to the membrane fractions from rabbit arteries. The KD values for [125I]-HEAT were also identical. However, Bmax varied considerably among rabbit arteries. There was a positive correlation between the logarithm of Bmax and the pD2 values for norepinephrine. The present results suggest that the regional difference in the pD2 values for norepinephrine in rabbit arteries is due to variations in the affinities to the al-adrenoceptors as well as the receptor densities.Remarkable differences have been detected in the sensitivity of isolated vascular smooth muscles to norepinephrine. Some of these dif ferences may be at least partly related to the difference in subtypes of a1-adrenoceptors. Recently, a regional difference in the nor epinephrine sensitivity, the pD2 value (a nega tive logarithm of a molar concentration pro ducing a half maximum response), of the drugs was reported in both arteries and veins. The affinity of norepinephrine to the a1-adre noceptors, the pKA values (the negative loga rithm of dissociation constant), was the pri mary determinant of sensitivity (pD2 values) to these drugs in the arteries from rabbits (1 3) and dogs (4). In contrast, the regional dif ference in sensitivity (pD2 value) for norepi nephrine in canine veins was related to the total concentration of the al-adrenoceptors or receptor density, but not to the affinity (pKA value) of norepinephrine to the a1-adre noceptors (5). Therefore, Takayanagi et al. (4) concluded that there is a qualitative differ ence between the al-adrenoceptor mechanisms

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