Platelet alpha 2 adrenoceptors in human and canine narcolepsy.
We have recently established that canine narcolepsy (an autosomal recessive genetic model of the human disorder) is dramatically improved by treatment with alpha 2 antagonists such as yohimbine (Nishino et al: J Pharmacol Exp Ther 253:1145-1152, 1990). To further investigate the role of alpha 2 adrenoceptors in narcolepsy, receptors labeled with [3H] yohimbine were examined on platelets from human and canine narcoleptic subjects. Twenty-eight Doberman pinschers were studied, 7 controls (C), 7 heterozygous (Hz), and 14 narcoleptics (N) (age and sex matched), including eight animals born in a backcross setting (narcoleptic x heterozygous; 5 narcoleptics and 3 heterozygous). The Kd and Bmax of each group respectively, were as follows: C, Kd = 2.86 +/- 0.76 nmol/L, Bmax = 295.78 +/- 31.89 fmol/mg protein; Hz, Kd = 2.06 +/- 0.23 nmol/L, Bmax = 307.02 +/- 22.21 fmol/mg protein; and N, Kd = 2.72 +/- 0.45 nmol/L, Bmax = 267.52 +/- 19.47 fmol/mg protein. No statistical differences were found between groups using nonparametric (Kruskall-Wallis) statistical procedures, and there were no correlations between any binding parameter and symptom severity within the narcoleptic group. Platelet alpha 2 receptor affinity and density also did not differ between narcoleptic and heterozygous dogs in the backcross litter (N [n = 5], Kd = 1.94 +/- 0.59 nmol/L, Bmax = 290.6 +/- 64.7 fmol/mg protein; Hz [n = 3], Kd = 2.83 +/- 0.47 nmol/L, Bmax = 294.2 +/- 42.9 fmol/mg protein). Fourteen human subjects, seven control and seven narcoleptic patients (age and sex matched), were included in the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Valtier
D
D
Sleep Research Center, Stanford University School of Medicine, Palo Alto, CA 94304.
Nishino
S
S
Guilleminault
C
C
Dement
W C
WC
Mignot
E
E
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology*; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000503:physiopathology*; D009638:Norepinephrine / Q000097:blood*; D011941:Receptors, Adrenergic / Q000502:physiology*; D015016:Yohimbine / Q000493:pharmacokinetics
D011941:Receptors, Adrenergic; D015016:Yohimbine; D009638:Norepinephrine