Evidence against a peripheral role of tachykinins in the initiation of micturition reflex in rats.
This study investigates the role of peripheral tachykinin receptors in the initiation of reflex urinary bladder contractions in urethane-anesthetized rats. Intravenous administration of the selective tachykinin neurokinin (NK)-1 receptor agonist [Sar9]substance P (SP) sulfone (0.3-30 nmol/kg) or of the selective tachykinin NK-2 receptor agonist [beta Ala8]NK-A(4-10) (0.3-100 nmol/kg) produced dose-related bladder contractions. Among NK-3 receptor agonists, senktide (1-100 nmol/kg) was not effective; [MePhe7] NK-B (3-100 nmol/kg) induced bladder contraction, but the magnitude of the response was only 20 to 25% of that produced by NK-1 or NK-2 agonists. The NK-1 receptor antagonist GR 82,334 (0.1 mumol/kg i.v.) blocked the urinary bladder contraction induced by [Sar9]SP sulfone (1 nmol/kg i.v.), but not that induced by [beta Ala8]NK-A(4-10). On the contrary, the NK-2 receptor antagonist L 659,877 (0.1-1 mumol/kg i.v.) abolished the effect of [beta Ala8] NK-A(4-10) (1 nmol/kg i.v.), but failed to affect the response to [Sar9]SP sulfone. The combined administration of GR 82,334 (0.1 mumol/kg i.v.) and L 659,877 (1 mumol/kg i.v.) blocked the tonic bladder contraction induced by topical application of capsaicin in pelvic ganglionectomized rats (efferent response of sensory nerves), but did not affect the hexamethonium-sensitive phasic reflex bladder contractions evoked by capsaicin in sham-operated rats (chemonociceptive micturition reflex). GR 82,334 (0.1 mumol/kg i.v.) or L 659,877 (1 mumol/kg i.v.), alone or in combination, did not modify cystometric parameters of the volume-evoked micturition reflex.(ABSTRACT TRUNCATED AT 250 WORDS)
Lecci
A
A
Pharmacological Research Department, Menarini Pharmaceuticals, Florence, Italy.
Giuliani
S
S
Patacchini
R
R
Maggi
C A
CA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology; D010803:Physalaemin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D015320:Tachykinins / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D014554:Urination / Q000502:physiology*
D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; C073361:cyclo(Gln-Trp-Phe-Gly-Leu-Met); C079014:GR 82334; D010803:Physalaemin; D000109:Acetylcholine; D002211:Capsaicin