Showing papers by "Maria G. Belvisi published in 1988"

Effects and interactions of sensory neuropeptides on airway microvascular leakage in guinea-pigs.

Abstract: 1. We have studied the effect of the sensory neuropeptides substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) on microvascular permeability in guinea-pig airways in vivo and investigated whether CGRP would potentiate the effect of SP. We used the extravasation of intravenously-injected Evans blue dye as an index of permeability. 2. The tachykinins SP, NKA and NKB (0.025-5.0 nmol kg-1, i.v.) significantly (P less than 0.05) increased extravasation of dye in a dose-related manner and with a similar pattern of distribution; they were most potent in the trachea and main bronchi, less potent in the larynx and intrapulmonary airways, and had little significant effect in the bladder. 3. SP was significantly more potent in causing extravasation of dye than NKA or NKB with ED50 values (nmol kg-1) in the range 0.04-0.1, depending on the airway level, compared with values in the range 0.3-0.7 for the neurokinins. 4. CGRP (0.0025-2.5 nmol kg-1, i.v.) had no significant effect on microvascular permeability and did not potentiate SP-induced extravasation of dye. 5. Each neuropeptide decreased mean arterial blood pressure, indicating vasodilatation, in a dose-related manner. Co-injection of CGRP and SP produced additive decreases in arterial pressure. 6. We conclude that, in guinea-pig airways, tachykinins increase microvascular permeability via tachykinin receptors of the NK-1 sub-type (indicated by an order of potency of SP greater than NKA = NKB) on endothelial cells. The response appears to be related to mechanisms in addition to vasodilatation. The relevance of the responses to the tachykinins in asthma is discussed.

Opioid modulation of non‐cholinergic neural bronchoconstriction in guinea‐pig in vivo

Abstract: 1. Opioid receptors have been demonstrated on sensory fibres in the vagus nerve. Non-cholinergic (NC) neural bronchoconstriction in guinea-pig is due to release of neuropeptides from sensory nerve endings. We have therefore studied the effect of opioids on this NC bronchoconstriction in the anaesthetized guinea-pig. 2. Bilateral vagal stimulation (5 V, 5 ms, 10 Hz) caused reproducible bronchoconstriction in guinea-pigs which was reduced by atropine (1 mg kg-1), but the NC component was unaffected by hexamethonium (10 mg kg-1). 3. NC bronchoconstriction was reduced by morphine in a dose-dependent manner (ED50 = 132 micrograms kg-1 with a maximal inhibition of 79 +/- 2.1% at 1 mg kg-1). Yohimbine (0.5 mg kg-1) did not alter the inhibitory effect of morphine (1 mg kg-1). 4. The inhibitory effect of morphine was completely reversed by naloxone (1 mg kg-1) which had no effect on NC bronchoconstriction. Propranolol (1 mg kg-1) significantly increased the NC bronchoconstrictor response but did not significantly alter the inhibition by morphine. 5. The selective mu-opioid receptor agonist Tyr-(D-Ala)-Gly-(N-Me-Phe)-Glyol (DAGOL) was significantly more potent than morphine with an ED50 of 5.4 micrograms kg-1 and complete inhibition at 100 micrograms kg-1. The delta-agonist Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE) was less potent than DAGOL with an ED50 of 28 micrograms kg-1 and a maximal inhibition of only 50 +/- 5% at 100 micrograms kg-1. The delta-agonist Tyr4D-Pen)-Gly-Phe-D-Pen) (DPDPE) was less potent than DAGOL with an ED5o of 28pgkg-1 and a maximal inhibition of only 50 + 5% at lOOPgkg- . The Kappa-receptor agonist, U-50,488H had no inhibitory effect on the NC bronchoconstrictor response. 6. The bronchoconstrictor responses to exogenous substance P (25 pgkg- 1) or acetylcholine (25 pg kg- 1) were unaffected by morphine (500 pg kg- 1). 7. We conclude that opioids inhibit the NC bronchoconstrictor response to vagal stimulation via an action on mu-opioid receptors localized to sensory nerve endings in the airway.