ABSTRACT
Neonatal treatment of mice with opioid and dopamine antagonists (naloxone, haloperidol and sulpiride) failed to alter the in vitro responsiveness of vasa deferentia to opioid agonists in the adulthood. Single neonatal administration of some opioid or dopaminergic agonists, viz. Met-enkephalin and piribedil, tended to enhance the sensitivity of in vitro preparations to opioid agonists, tested in adult animals. Behavioural differences and late mortality were also observed.
Subject(s)
Dopamine/physiology , Endorphins/pharmacology , Vas Deferens/drug effects , Animals , Animals, Newborn , Enkephalin, Methionine/analogs & derivatives , Enkephalin, Methionine/pharmacology , Haloperidol/pharmacology , Male , Mice , Morphine/pharmacology , Naloxone/pharmacology , Piribedil/pharmacology , Sulpiride/pharmacology , Time FactorsABSTRACT
The inhibitory effects of various opiates on developing rat vas deferens were studied by determining the degree of depression of mechanical responses elicited by electrical field stimulation. All agonists showed decreased effects with maturation, but the decrease occurred at different times. With normorphine the loss of agonist activity was greatest at days 12-16, while with D-Met2,Pro5-enkephalinamide it was greatest at days 16-30. beta-Endorphin also was less effective in adult than 30-day preparations, but methionine enkephalin was ineffective at all ages. Morphine and normorphine were weak antagonists of opiate agonists in the adult preparations. These results indicate that the nature and pharmacologic sensitivity of opiate actions change with development.
Subject(s)
Endorphins/physiology , Muscle Contraction/drug effects , Receptors, Opioid/physiology , Vas Deferens/growth & development , Animals , Electric Stimulation , Endorphins/pharmacology , In Vitro Techniques , Male , Naltrexone/pharmacology , Rats , Receptors, Opioid/drug effects , Vas Deferens/metabolism , Vas Deferens/physiologyABSTRACT
The opioid activities of enkephalin analogues bearing D- or L-aminopentane-sulfonic/phosphonic acid at position 5 were studied in vitro, in electrically stimulated longitudinal muscle strip of guinea-pig ileum and mouse vas deferens preparations and in vivo in the rat tail-flick test. Using their in vitro effects Met-enkephalin-like, beta-endorphin-like, (nor)morphine-like and derivatives of intermediate character could be differentiated. Correlating the in vitro activities with the analgesic activity in vivo it is concluded that the enkephalin-like character in a pentapetide may hinder the expression of analgesic activity, when the compounds are given into the cerebroventricular system.
