ALTERED EXPRESSION OF DOPAMINE D2 RECEPTOR MESSENGER-RNA SPLICE VARIANTS IN BRAIN AND PITUITARY OF SPONTANEOUSLY HYPERTENSIVE RATS

Both central and peripheral dopamine (DA) has been shown to play a rol e in the regulation of blood pressure. Using sensitive nuclease protec tion analysis, we have compared the expression of DA D-2 receptor (D2- R) mRNA splice variants in brain and pituitary of spontaneously hypert ensive rats (SHR) with normotensive Wistar-Kyoto (WKY) controls. Level s of D2-R mRNA were significantly altered in pituitary anterior lobe ( AL) and neurointermediate lobe (NIL), and in striatum of SHR, but not in any other brain regions examined. SHR pituitary expressed 50-80% hi gher levels of D2-R mRNA, coupled with an increase in the relative pro portion of the long (D2-L) mRNA variant. In contrast, overall D2-R mRN A expression in SHR striatum was only 75% that of WKY controls, howeve r, the relative proportion of the D2-L splice variant was increased. T he present data demonstrate that tissue specific alterations in D2-R m RNA levels and primary transcript splicing exist in the SHR and sugges t that these changes may in part mediate differential responsiveness t o DA that may be related to the development of hypertension.