Role of tachykinin NK1 and NK2 receptors on colonic motility in anesthetized rats: effect of agonists.
Tachykinins fulfill general criteria to be considered as neurotransmitters-neuroeffectors in the mammalian enteric nervous system; however, little information is available about their role in the regulation of intestinal motility in vivo. The present study investigates the effect of selective tachykinin receptor agonists on colonic motility in urethane-anesthetized rats. Colonic motility was recorded by means of a balloon-catheter device (filled with 0.5 mL of water) inserted for 7 cm through the rectum. In atropine- and guanethidine-pretreated rats, the NK1 receptor agonist [Sar9]substance P sulfone (0.3-300 nmol/kg i.v.) dose dependently induced phasic contractions followed by an enhancement in the amplitude and frequency of spontaneous contractions. In three of six cases, a transient inhibition (3-5 min) of spontaneous motility was also evident after the phasic contraction. All these effects were reduced by the NK1 receptor antagonist SR 140333 (1 mumol/kg i.v.). In atropine- and guanethidine-pretreated rats and in the presence of SR 140333 (1 mumol/kg i.v.), the NK2 receptor agonist [beta-Ala8]neurokinin A-(4-10) (0.3-300 nmol/kg i.v.) induced a dose-dependent tonic contraction, but the amplitude and frequency of spontaneous contractions were not changed. NK2 receptor antagonists such as MEN 11420 (0.01-1 mumol/kg i.v.), MEN 10627 (1 mumol/kg i.v.), or SR 48968 (1 mumol/kg i.v.) reduced the effect of [beta-Ala8]neurokinin A-(4-10). The present results indicate that NK2 receptor stimulation evokes a pure excitatory effect on colonic motility whereas NK1 receptor stimulation induces both excitatory and inhibitory effects.
Lecci
A
A
Menarini Ricerche, Pharmacology Research Department, Florence, Italy.
Tramontana
M
M
Giuliani
S
S
Maggi
C A
CA
D000758:Anesthesia; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology; D011812:Quinuclidines / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000819:agonists* / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000819:agonists* / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D001549:Benzamides; C107754:MEN 11420; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C062618:substance P, Sar(9)-Met(O2)(11)-; C064218:neurokinin A (4-10), beta-Ala(8)-; C085215:SR 140333; C090951:MEN 10627; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A