The objective of this study was to determine if dexmedetomidine (dex) a selective n% agonist, inhibits Pp in the rat CCD when P p is stimulated by the nonhydrolyzable cyclic-AMP analog 8-p-(chlorophenylthio) cychc AMP (CPTcAMP). Pp was determined in Sprague-Dawley rat CCDs via the isolated perfused tubule technique. CPT-cAMP at IO-4M added to the bath raised Pp (fun/sec) from 0 to 651±75 (p< .001) (n=6). Dex at 100 nM added to the bath lowered Pp to 396±92 (p<.05). The addition of 100 nM atipamezole (ati), a selective 02 antagonist, raised Pp to 526±114, These data substantiate previous findings showing that epinephrine inhibits bromoadenosine-cAMPstimulated Pp via an ag mechanism (Hawk et al., Am. J. Physiol. 265:F449, 1993). We also measured dex-induced inhibition of arginine vasopressin (AVP)-stimulated Pp in the presence of the protein kinase C (PKC) inhibitor staurosporine (ST). AVP at 220 pM added to the bath raised Pp from 0 to 605±82 (p<.001) (n=6). Dex at 100 nM with 10'-4 ST in the bath lowered Pp to 145±31 and the addition of 100 nM ati raised Pp to 558±103. Thus, dex reduced AVP-stimulated Pp by 76%, not 100% as previously reported without ST in the bath (Rouch & Kudo, FASEB J. 8:A551, 1994). We conclude that dexmedetomidine significantly inhibits P p in the rat CCD in the presence of constant cellular cAMP levels. This indicates that second messengers other than cAMP are involved in 2 inhibition of Pp and one such messenger could be PKC. This study was supported by NSF grant IBN 9507444.
|State||Published - 1996|