In vivo pharmacology of [beta Ala8]neurokinin A-(4-10), a selective NK-2 tachykinin receptor agonist.
We studied the effect of [beta Ala8]neurokinin A-(4-10), a newly developed selective NK-2 tachykinin receptor agonist, on various parameters in anaesthetized rats (blood pressure, urinary bladder motility, plasma extravasation) and guinea-pigs (salivation, increase of pulmonary insufflation pressure) as compared to the response produced by tachykinins. [beta Ala8]Neurokinin A-(4-10) was as active as, or more active than, neurokinin A (NKA) or NKA-(4-10) in producing rat bladder contraction or bronchospasm in guinea-pigs, two effects known to involve activation of NK-2 receptors. On the other hand, the synthetic peptide was weakly active, if active at all, in producing hypotension or plasma extravasation in the rat bladder as well as salivation in guinea-pigs, effects known to involve activation of NK-1 receptors. These findings provide evidence that [beta Ala8]NKA-(4-10) acts as a selective NK-2 agonist in vivo and that it can be used to explore the distribution and function of NK-2 receptors.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Giuliani
S
S
Ballati
L
L
Rovero
P
P
Abelli
L
L
Manzini
S
S
Giachetti
A
A
Meli
A
A
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012472:Salivation / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects
D001798:Blood Proteins; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C064218:neurokinin A (4-10), beta-Ala(8)-; D015288:Neurokinin A; C056408:neurokinin A(4-10)