Tyr-D-Arg2-Phe-sarcosine4 (TAPS), a mu-selective tetrapeptide analog of
dermorphin, induced sustained antinociception and stimulated ventilatory minute volume (MV) at the doses of 3 to 100 pmol i.c.v. The doses of 30 and 100 pmol i.c.v. induced
catalepsy. The effect of TAPS on MV was in negative correlation with the dose and the maximal response was achieved by the lowest (3 pmol) dose (+63 +/- 23%, P < .05).
Morphine, an agonist at both mu 1 and mu 2 sites, at a dose of 150 nmol i.c.v. (equianalgesic to 100 pmol of TAPS decreased the MV by 30%, due to a decrease in ventilatory tidal volume. The antinociceptive effect of TAPS was antagonized by
naloxone and the mu 1 receptor antagonist,
naloxonazine.
Naloxonazine also attenuated the
catalepsy produced by 100 pmol of TAPS i.c.v. and the respiratory stimulation produced by 3 pmol of TAPS i.c.v. Pretreatment with 30 pmol of TAPS antagonized the
respiratory depression induced by the mu
opioid agonist
dermorphin (changes in MV after
dermorphin alone at 1 or 3 nmol were -22 +/- 10% and -60 +/- 9% and, after pretreatment with TAPS, +44 +/- 11% and -18 +/- 5%, respectively). After combined pretreatment with
naloxonazine and TAPS, 1 nmol of
dermorphin had no significant effect on ventilation. In contrast, pretreatment with a low
respiratory stimulant dose (10 pmol i.c.v.) of
dermorphin did not modify the effect of 1 nmol of
dermorphin. In conclusion, the antinociceptive, cataleptic and
respiratory stimulant effects of TAPS appear to be a related to its agonist action at the mu 1
opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)