Neurokinins induce a relaxation of the rat duodenum "in vivo" by activating postganglionic sympathetic elements in prevertebral ganglia: involvement of an NK-2 type of neurokinin receptor.
In the small intestine of urethane-anesthetized rats, i.v. neurokinins (NKs) (0.043-14 nmol/kg) produce three distinct motor effects, e.g.: 1) a transient relaxation followed by 2) a phasic contraction and 3) a tonic contraction. The aim of this study was to characterize the nature of the receptor determining the transient relaxation and mechanisms involved. The transient relaxation was more evident in the distal than in the proximal duodenum or in the jejunum. The rank order of potency of NKs in producing relaxation was NKA greater than substance P greater than NKB. The heptapeptide NKA(4-10) was as potent as the decapeptide NKA in determining relaxation but less potent than NKA in producing phasic or tonic contraction. NKA (0.43 nmol/kg i.v.)-induced relaxation and tonic contraction were unaffected by [D-Pro2, D-Trp7.g]substance P, a compound which, in this tissue, acts as a NK-1 receptor antagonist. NKA (0.43 nmol/kg i.v.)-induced relaxation of the distal duodenum was unaffected by atropine, hexamethonium or adrenalectomy, reduced by phentolamine plus propranolol and abolished by guanethidine or acute (15 min before) removal of the celiac ganglion complex. These findings are consistent with the hypothesis that activation of a NK-2 receptor located on postganglionic sympathetic neurons in the prevertebral ganglia produces the intestinal relaxation in response to i.v. NKs.
Giuliani
S
S
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Maggi
C A
CA
Rovero
P
P
Meli
A
A
D000315:Adrenalectomy; D000818:Animals; D004386:Duodenum / Q000187:drug effects* / Q000294:innervation; D006145:Guanethidine / Q000494:pharmacology; D015286:Kassinin; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D015288:Neurokinin A; D015287:Neurokinin B; D009479:Neuropeptides / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology*
D009479:Neuropeptides; D009842:Oligopeptides; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D013373:Substance P; D015286:Kassinin; D015288:Neurokinin A; D015287:Neurokinin B; D011433:Propranolol; D009638:Norepinephrine; D010646:Phentolamine; D006145:Guanethidine