The Responses of Autonomically-Innervated Smooth Muscle to Nerve Stimulation and to Drugs

Wardle, Kay Alison (1987) The Responses of Autonomically-Innervated Smooth Muscle to Nerve Stimulation and to Drugs. PhD thesis, University of Glasgow.

Abstract

1. The intracellular electrical and mechanical responses of the rabbit ear artery, the rabbit superior mesenteric artery and the mouse vas deferens were examined in response to field stimulation of intramural nerves and to drugs. Each tissue demonstrated co-transmission involving noradrenaline (NA) and adenosine 5'-triphosphate (ATP), or a closely related nucleotide. 2. In the rabbit ear artery, the rabbit mesenteric artery and the mouse vas deferens the electrical response evoked by field stimulation consisted of excitatory junction potentials (e. j. p. s), which facilitated and summated to fire action potentials. These e. j. p. s were abolished by a,B-methylene ATP (a,B MeATP, 1-10 x 10-6M), suggesting that they were mediated by ATP. Only in the rabbit ear artery was there an additional electrical event mediated by NA. This took the form of a small, slow membrane depolarization which followed the e. j. p. s and which was antagonized by the a-adrenoceptor antagonists phentolamine (1 x 10-6M) or prazosin (1 x 10-7M). 3. In each of these tissues, all electrical and mechanical responses to field stimulation were abolished by either tetrodotoxin (TTX, 1 x 10-6M) or guanethidine (1 x 10-6M), suggesting that they were due to transmitters released from sympathetic nerves. 4. In the mouse vas deferens and rabbit mesenteric artery, both transmitters (NA and ATP) played a role in the contractile response to field stimulation. In the rabbit ear artery, however, only NA appeared to mediate a contractile event. 5. Contractile responses to nerve-released ATP were accompanied by a change in membrane potential. Na+ and K+ appeared to be the main ions underlying the e. j. p. and action potential. In contrast, contractile responses evoked by NA appeared to be mediated by both voltage-dependent and voltage-independent mechanisms, the relative contribution of each to the overall response varying from one tissue to another. 6. In the mouse vas deferens, exogenous application of ATP (1 x 10-4 - 1 x 10-3M) or its stable analogue, a,BMeATP (1 x 10-6M) by pressure ejection from a micro-pipette produced dose dependent depolarizations. NA (1 x 10-4 - 1 x 10-3M), similarly applied produced no such change in membrane potential. 7. In the mouse vas deferens, local application of bradykinin (1-100 x 10-7M) produced small, slow membrane hyperpolarizations. VIP (1-100 x 10-7M), neuropeptide Y (1-100 x 10-7M), substance P (1-100 x 10-7M), leu-enkephalin (1-100 x 10-7M), met-enkephalin (1-100 x 10-7M), somatostatin (1-100 x 10-7M) and bombesin (1-100 x 10-7M), similarly applied, each produced no significant change in membrane potential. None of these peptides, it was concluded, appear to be the transmitter mediating the e. j. p. s in this tissue. 8. In the rat anococcygeus muscle, membrane potential changes recorded intracellularly following field (transmural) or extrinsic nerve stimulation were indistinguishable. Single stimuli usually produced a slow depolarization; trains of pulses produced a fast e. j. p. initially, followed by a slow depolarization similar to that produced by single pulses. The fast e. j. p. s, the slow depolarizations and the accompanying contractions were abolished by the a-adrenoceptor antagonists phen-tolamine (1 x 10-6) or prazosin (1 x 10-7M), by TTX (1 x 10-6M), but were unaffected by a,BMeATP (1 - 10 x 10-6M) . 9. Application of NA (1 x 10-8 - 1 x 10-6M) by pressure ejection from a micro-pipette to the rat anococcygeus muscle depolarized the membrane and produced localized contractions, both of which were abolished by phentolamine (1 x 10-6M) or prazosin (1 x 10-7M). 10. Application of ATP (1 x 10-4 - 1 x 10-3M) by pressure ejection to the rat anococcygeus muscle produced small membrane depolarizations and localized contractions which were unaffected by phentolamine (1 x 10-6M) or prazosin (1 x 10-7M), but abolished by a,BMeATP (1 x 10-6M). 11. Results from experiments on the rat anococcygeus muscle show that field or extrinsinc nerve stimulation released only one excitatory transmitter, namely NA, although receptors for both NA and ATP are present on this muscle and that there was no evidence for excitatory cotransmission in this tissue. (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Pharmacology
• Date of Award: 1987
• Depositing User: Enlighten Team
• Unique ID: glathesis:1987-77590
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2020 09:04
• Last Modified: 14 Jan 2020 09:04
• URI: https://theses.gla.ac.uk/id/eprint/77590