JaaVa rictnnagi Rjtcn Prrss Lid_Nc York Yurukcinisr} 194_ Intcrnaloni ercicty M Regulation of Tyrosine Hydroxylase Gene Expression in the Rat Carotid Body by Hypoxia #fMaria F Czyzyk-Krzeska; *Douglas A. Bayliss; #Edward E: Lawson: and "#David E Millhorn Lutaratory Wf .ulekular und Drrelopmutal Neurosciencc; Physiolvgt' uud tPcdiatrics fC urriculum Oenarierin Ncnrobiolegs: Umversity Wf Vonth Cardlina Chapet Hill. Chupl Hill,  Vonth Carolina, Abstract: The activily (V, of tyrosine hydroxylax (TH; cervical ganglion adrena medulla. The inctease EC [.14.16.2) the rate limiting enzyme Ihz synthesis of mRNA in carolid body during hypoxia did nOt requin carolid body  superior cervical Clccnclmincs neraton 0l the crorid body intact adrenal giands Unertictu additian, hypercapnia. inothzr physiological ganglion: and Ihe adrena mccullj dunng hypoxia (LE,, Tc- 5uimulus P.Oz} The present study was undenuaken rolid body aclivity. failed cucco uclermine inducc wn intTcas - TH mRI ; il the TH aclivity thcsc tissucs during hypoxia cclls Our iindings sugeest that hypoxix stimulak ~ in tpe ncrtal is regulaled at the level OfTH mRNA Adult rats Wcre exposed gene cxpression the carotid body bY Inecnunt to hypoxia (103 02) Iading Jir for periods thot cells Key Words: Tyrosine hyanu Utom Iype Keun dlrnsic 48 h. Thc carotid bodics supcror cervical ganglia and ylasc_Carotid Hxpoxia Gene cxpression_M body aJrenals #ere remaved and processcd for in situ hybndization RNA-In silu hybrdization. Czyzyk-Rrzeska H enger using "S-Iabcled oligonucleutide probcs The conccntralion Regulation trosire hedroxylase Eene expression of TH mRNA was increased by hypoxim aall iime points Neurtk hem Inc rt corotid body by h;poxia 58. 03i body type cells  but not cells o cither supzrior Grond 1546 ([992}. The    respiratory and cardiovascular in carolid body (Hanbaucr: 1977: Hanbauer neuronai This partial 1977; Gonzalez et al,, 1979, [984) sponses [0 systemic hypoxia (i.e reduction in Increast" pressure of oxyecn arerial blood; P,o-) emanate TH activity Vra ] due [0 an increase the afini primarily (rom thc carolid botuchemorccnlors which of TH for its tetrahydropterin cofactor (Kn) is located bilaterally at the bifurcation o the common changed during hypoxia (Hanbaucr ctal. 1977) H; carotid artcry (Heymans and Neil, [958) Stimulation oxia also causes an increase in TH aclivity (V 72) of the carolid body by hypoxia causcs hyperventilation sympathetic postganglionic neurons (Gonzalcz et (Heymans and Neil, 1958) and numbcr cardio 1979} and cclls of thc adrenal medulla (Hayashi ct : 19901. vascular effects that are mediated by Ihe sympathctic nervous system (Liltle and 1975}. It is Oberg The present study wis undertaken I0 lest Ihc He known that hypoxia rauscs carotid body type cclls to polhesis that the increased TH activity in the caro: depolarize Delpiano and Hescheler; /989) and release body, sympathetic ganglia and adrenal medulla ce the catecholamine neurotransmitter dopamine (Fidone regulated at the level of TH mRN; dunng hypoxia [985; Rigual et al , 1986). 1982: Fishman et al; We report here that exposure t0 hypoxia (1-48 addition; biochemical studies have revealed that the TH mRNA in rai carotid bod: causedan lncreacein aclivily ol tyrosinc hydroxylasc [TH: L-tyrosine but not in either the superior cervical sympathetic gan tcla The increase in TH mRN: hydropterdine: oxygen oxidoreductase (3-hydroxylat- adrenal medulla glia ing) , EC 1.1[4.16.2], the rate-limiting enzyme the in the carotid body during hypoxia did not depend on biosynihesis of catecholamines enhanced by hypoxia innervation of the carolid body by cithcr sensory 22, 199|; reviscd manuscnpt reccivcd Scplcmbcr Abhrerlullons uscd: PBS, phosphalc-bullcred slinc, SSC . suline- Rescitcd ay jcccplcd Scplcmbcr 27. 1S9L sodium ciinic: TH. tyrosine hydrox;las Addrcss concpcndcnce ar]cprint rcqucsis t0 Dr M Crytyi- "Physiology, University of North Carolina Koeki Dcpinineni Chapcl Hill, Chape| Hill; NC 17599-7545,USA 1538 hyeAcapnia LXW tBleed Co? iN
JaaVa rictnnagi Rjtcn Prrss Lid_Nc York 194_ Intcrnaloni ercicty M Yurukcinisr} Regulation of Tyrosine Hydroxylase Gene Expression in the Rat Carotid Body by Hypoxia #fMaria F Czyzyk-Krzeska; *Douglas A. Bayliss; #Edward E: Lawson: and "#David E Millhorn Lutaratory Wf .ulekular und Drrelopmutal Neurosciencc; Oenarierin Physiolvgt' uud tPcdiatrics fC urriculum Ncnrobiolegs: Umversity Wf Vonth Cardlina Chapet Hill. Chupl Hill,  Vonth Carolina, Abstract: The activily (V, of tyrosine hydroxylax (TH; EC [.14.16.2) the rate limiting enzyme Ihz synthesis of Clccnclmincs Unertictu carolid body  superior cervical ganglion: and Ihe adrena mccullj dunng hypoxia (LE,, Tc- cucco P.Oz} The present study was undenuaken uclermine il the ncrtal TH aclivity thcsc tissucs during hypoxia is regulaled at the level OfTH mRNA Adult rats Wcre exposed to hypoxia (103 02) Keun Jir for periods Iading Utom 48 h. Thc carotid bodics supcror cervical ganglia and aJrenals #ere remaved and processcd for in situ hybndization using "S-Iabcled oligonucleutide probcs The conccntralion of TH mRNA was increased by hypoxim aall iime points Grond body type cells  but not cells o cither supzrior cervical ganglion adrena medulla. The inctease mRNA in carolid body during hypoxia did nOt requin neraton 0l the crorid body intact adrenal giands additian, hypercapnia. inothzr physiological 5uimulus rolid body aclivity. failed inducc wn intTcas - TH mRI ; in tpe cclls Our iindings sugeest that hypoxix stimulak ~ gene cxpression the carotid body bY Inecnunt  thot dlrnsic Iype cells Key Words: Tyrosine hyanu ylasc_Carotid body Hxpoxia Gene cxpression_M enger RNA-In silu hybrdization. Czyzyk-Rrzeska H Regulation trosire hedroxylase Eene expression Inc rt corotid body by h;poxia Neurtk hem 58. 03i 1546 ([992}. The    respiratory and cardiovascular neuronai sponses [0 systemic hypoxia (i.e reduction in partial pressure of oxyecn arerial blood; P,o-) emanate primarily (rom thc carolid botuchemorccnlors which located bilaterally at the bifurcation o the common carotid artcry (Heymans and Neil, [958) Stimulation of the carolid body by hypoxia causcs hyperventilation (Heymans and Neil, 1958) and numbcr cardio vascular effects that are mediated by Ihe sympathctic nervous system (Liltle and Oberg 1975}. It is He known that hypoxia rauscs carotid body type cclls to depolarize Delpiano and Hescheler; /989) and release the catecholamine neurotransmitter dopamine (Fidone 1982: Fishman et al; [985; Rigual et al , 1986). addition; biochemical studies have revealed that the aclivily ol tyrosinc hydroxylasc [TH: L-tyrosine tcla hydropterdine: oxygen oxidoreductase (3-hydroxylat- ing) , EC 1.1[4.16.2], the rate-limiting enzyme the biosynihesis of catecholamines enhanced by hypoxia in carolid body (Hanbaucr: 1977: Hanbauer 1977; Gonzalez et al,, 1979, [984) This Increast" TH activity due [0 an increase Vra ] the afini of TH for its tetrahydropterin cofactor (Kn) is changed during hypoxia (Hanbaucr ctal. 1977) H; oxia also causes an increase in TH aclivity (V 72) sympathetic postganglionic neurons (Gonzalcz et 1979} and cclls of thc adrenal medulla (Hayashi ct : 19901. The present study wis undertaken I0 lest Ihc polhesis that the increased TH activity in the caro: body, sympathetic ganglia and adrenal medulla ce dunng hypoxia regulated at the level of TH mRN; We report here that exposure t0 hypoxia (1-48 causedan lncreacein TH mRNA in rai carotid bod: but not in either the superior cervical sympathetic gan glia adrenal medulla The increase in TH mRN: in the carotid body during hypoxia did not depend on innervation of the carolid body by cithcr sensory Rescitcd ay 22, 199|; reviscd manuscnpt reccivcd Scplcmbcr jcccplcd Scplcmbcr 27. 1S9L Addrcss concpcndcnce ar]cprint rcqucsis t0 Dr M Crytyi- Koeki Dcpinineni "Physiology, University of North Carolina Chapcl Hill, Chape| Hill; NC 17599-7545,USA Abhrerlullons uscd: PBS, phosphalc-bullcred slinc, SSC . suline- sodium ciinic: TH. tyrosine hydrox;las 1538 hyeAcapnia LXW Co? iN tBleed