Tomomi Yamaguchi (1), Kouki Kitagawa (2) and Yasushi Kuraishi (1,*)
(1) Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences,
Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194,
Japan
(2) Department of Bioorganic and Medicinal Chemistry, Niigata College of
Pharmacy, 5-13-2 Kamishin'ei-cho, Niigata 950-2081, Japan
(*) To whom correspondence should be addressed.
Abstract: Endomorphin-1 and endomorphin-2 are newly identified
endogenous peptides and have high affinity and selectivity for mu-opioid
receptors. The present experiments were conducted to determine whether intracisternal
injection of these peptides would produce an itch-associated response and
antinociception and to compare their effects to that of morphine. Endomorphin-1
and endomorphin-2 (0.3 - 3 nmol/mouse) elicited facial scratching characterized
by bell-shaped dose-response curves with a peak effect at endomorphin-1
at 0.3 nmol/mouse and endomorphin-2 at 1 nmol/mouse. Their peak effects
were inhibited by subcutaneous pretreatment with naloxone (1 mg/kg). Morphine
(0.3 - 30 nmol/mouse) produced facial scratching, and its dose-response
curve was also bell-shaped. Scratching of the body trunk, head and ears
were not elicited by these doses of endomorphins and morphine. Endomorphin-1
and -2 at doses of 0.3 - 3 nmol/mouse produced dose-dependent antinociception,
as measured with the tail-pressure test. The potency and duration of actions
of these peptides were comparable to those of morphine. The results suggest
that endomorphin-1 and endomorphin-2 are involved in itch-signaling and
pain-inhibiting functions of the brain.
Keywords: Endomorphin-1 and -2, Facial scratching, Itch, Analgesia, Intracisternal
injection